Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development
Abstract
:1. Introduction
2. Exosomal miRNAs and Intestinal Maturation
2.1. Intestinal Epithelial Cells
2.2. Intestinal Stem Cells
2.3. Intestinal Epithelial Barrier Function
2.3.1. Tight Junctions
2.3.2. Goblet Cells and Mucus Layer
2.3.3. Gut Microbiome
2.4. Lamina Propria Regulatory T Cells
2.4.1. Epigenetic Regulation of FOXP3 Expression
2.4.2. Transforming Growth Factor β and FOXP3 Expression
2.5. Anti-Inflammatory Action of Milk Exosomes
2.6. Adaptive Maternal Responses of Milk Exosomes in Preterm Infants
3. Necrotizing Enterocolitis
3.1. Pathogenesis
3.2. Milk Exosomes in Experimental Necrotizing Enterocolitis
3.3. Anti-Inflammatory Action of miRNA-148a, miRNA-22 and miRNA-30b
3.4. Hormonal Regulation of MiRNA-148a Expression
3.5. MEX-Mediated Up-Regulation of TNF-α-Induced Protein 3
3.6. Milk Exosome Lipidomics and NEC Prevention
3.7. Improvement of Malnutrition-Induced Intestinal Barrier Dysfunction
4. Systemic Bioavailability of Milk Exosomes for Epigenetic Regulation
4.1. Milk Exosomes, Thymic T-Cell Maturation and Atopy Prevention
4.2. Milk Exosomes and Hepatic Metabolism
4.3. Milk Exosomes and Neurodevelopment
4.4. Milk Exosomes and Potential Impact on Pancreatic β-Cell Proliferation
4.5. Milk Exosomes and Their Potential Impact on Beige/Brown Adipogenesis
4.6. Milk Exosomes and Their Potential Impact on White Adipogenesis
4.7. Milk Exosomes and Bone Homeostasis
5. Milk Processing and Exosome Bioavailability
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations (in Alphabetical Order)
AD | atopic dermatitis |
AMPK | adenosine monophosphate-activated protein kinase |
α-syn | α-synuclein |
BAT | brown adipose tissue |
BCAA | branched-chain amino acid |
BCKD | branched-chain α-ketoacid dehydrogenase |
BET | beige adipose tissue |
BLG | β-lactoglobulin |
BMI | body mass index |
BMMF | bovine meat and milk factor |
CAV3 | caveolin 3 |
CaMKIIα | calcium/calmodulin-dependent protein kinase IIα |
CARMA1 | CARD-containing MAGUK protein 1 |
CCK | cholecystokinin |
CCKR | cholecystokinin receptor |
CCR | chemokine, CC motif, receptor |
CDX2 | caudal-type homeobox transcription factor 2 |
CEBP | CCAAT/enhancer-binding protein |
CIDEA | death-inducing DFFA-like effector A |
circRNA | circular RNA |
CLDN1 | claudin 1 |
CMA | cow milk alllergy |
CRC | colorectal cancer |
CYR61 | cystein-rich protein 61 |
DBT | dihydrolipoamide branched-chain transacylase |
DC | dendritic cell |
DMBT1 | deleted in malignant brain tumors 1 |
DNMT1 | DNA methyltransferase 1 |
DON | deoxynivalenol |
DSS | dextran sodium sulfate |
ERRα | estrogen-related receptor-α |
ER | endoplasmic reticulum |
EV | extracellular vesicle |
FcRn | neonatal crystallizable fragment receptor |
FOXP3 | forkhead box transcription factor P3 |
GATA4 | GATA-binding protein 4 |
GI | gastrointestinal tract |
GP130 | interleukin 6 signal transducer |
GRP94 | glucose-regulated protein 94 |
GSIS | glucose-stimulated insulin secretion |
GSK3 | glycogen synthase kinase 3 |
HM | human milk |
HDAC4 | histone deacetylase 4 |
hMSC | human mesenchymal stem cell |
HoP | Holder pasteurization |
HSP | heat shock protein |
IBD | inflammatory bowel disease |
IEC | intestinal epithelial cell |
IFN | interferon |
IgA | immunoglobulin A |
IgG | immunoglobulin G |
IGF-1 | insulin-like growth factor 1 |
IGF1R | IGF-1 receptor |
IκB | inhibitor of κB |
IKK | IκB kinase |
IL-1 | interleukin 1 |
IL-2 | interleukin 2 |
IL-6 | interleukin 6 |
IL-8 | interleukin 8 |
IL-10 | interleukin 10 |
IL-17 | interleukin 17 |
ISC | intestinal stem cell |
iTreg | inducible regulatory T cell |
LDLR | low density-lipoprotein receptor |
LGR5 | leucine-rich-repeat-containing G-protein-coupled receptor 5 |
lncRNA | long non-coding RNA |
LRP6 | low-density lipoprotein receptor-related protein 6 |
MesD | mesoderm development |
MEV | milk extracellular vesicle |
MEX | milk exosome |
MFG | milk fat globule |
MFG-E8 | MFG epidermal growth factor 8 |
MGEC | mammary gland epithelial cell |
MHC | major histocompatibility complex |
miRNA | micro-ribonucleic acid |
MPO | myeloperoxidase |
mTORC1 | mechanistic target of rapamycin complex 1 |
MUC1 MUC2 | mucin 1 mucin 2 |
MyD88 | MyD88 innate immune signal transduction adaptor |
NCOA1 | nuclear receptor co-activator 1 |
NEC | necrotizing enterocolitis |
NF-κB | RELA protooncogene, NFKB subunit |
NK | natural killer |
OCLN | occludin |
OTU | operational taxonomic unit |
PBMC | peripheral blood mononuclear cell |
PCNA | proliferating cell nuclear antigen |
PGC-1α | peroxisome proliferator-activated receptor-γ co-activator 1α |
PGC-1β | peroxisome proliferator-activated receptor-γ co-activator 1β |
PI3K | phosphatidylinositol 3-kinase |
PPAR | peroxisome proliferator-activated receptor |
PPARGC1A | peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) |
PRKAA1 | catalytic subunit α1 of AMPK |
PRKAG2 | regulatory subunit γ2 of AMPK |
PTEN | phosphatase and tensin homolog |
PURB | purine-rich element binding protein B |
RIP140 | receptor interacting protein 140 |
RegIIIγ | regenerating islet-derived 3γ |
ROR | RAR-related orphan receptor |
SIRT1 | sirtuin 1 |
SNARE | soluble N-ethylmaleimide-sensitive factor attachment protein receptor |
SOCS1 | signal transducer and activator of transcription 1 |
SNCA | α-synuclein |
STAT | signal transducer and activator of transcription |
TCR | T cell receptor |
TGFβ | transforming growth factor-β |
TJ | tight junction |
TLR | toll-like receptor |
TNFα | tumor necrosis factor-α |
TNFAIP3 | TNFα-induced protein 3 |
TFF3 | trefoil factor 3 |
T2DM | type 2 diabetes mellitus |
Treg | FOXP3+ regulatory T cell |
TSDR | Treg-specific demethylated region |
TSG101 | tumor susceptibility gene 101 |
UCP1 | uncoupling protein 1 |
UCP2 | uncoupling protein 2 |
UCP3 | uncoupling protein 3 |
UHT | ultraheat-treated |
3′UTR | 3′-untranslated region |
VEGF | vascular endothelial growth factor |
WAT | white adipose tissue |
WNT | wingless |
ZO-1 | zonula occludens 1 |
References
- Renz, H.; Brandtzaeg, P.; Hornef, M. The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nat. Rev. Immunol. 2011, 12, 9–23. [Google Scholar] [CrossRef] [PubMed]
- Zonneveld, M.I.; van Herwijnen, M.J.C.; Fernandez-Gutierrez, M.M.; Giovanazzi, A.; de Groot, A.M.; Kleinjan, M.; van Capel, T.M.M.; Sijts, A.J.A.M.; Taams, L.S.; Garssen, J.; et al. Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses. J. Extracell. Vesicles 2021, 10, e12071. [Google Scholar] [CrossRef] [PubMed]
- Carr, L.E.; Virmani, M.D.; Rosa, F.; Munblit, D.; Matazel, K.S.; Elolimy, A.A.; Yeruva, L. Role of human milk bioactives on infants’ gut and immune health. Front. Immunol. 2021, 12, 604080. [Google Scholar] [CrossRef] [PubMed]
- Victora, C.G.; Bahl, R.; Barros, A.J.; França, G.V.; Horton, S.; Krasevec, J.; Murch, S.; Sankar, M.J.; Walker, N.; Rollins, N.C.; et al. Breastfeeding in the 21st century: Epidemiology, mechanisms, and lifelong effect. Lancet 2016, 387, 475–490. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; John, S.M.; Schmitz, G. Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth. Nutr. J. 2013, 12, 103. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C. Milk—A nutrient system of mammalian evolution promoting mTORC1-dependent translation. Int. J. Mol. Sci. 2015, 16, 17048–17087. [Google Scholar] [CrossRef]
- Melnik, B.C.; Kakulas, F.; Geddes, D.T.; Hartmann, P.E.; John, S.M.; Carrera-Bastos, P.; Cordain, L.; Schmitz, G. Milk miRNAs: Simple nutrients or systemic functional regulators? Nutr. Metab. 2016, 13, 42. [Google Scholar] [CrossRef] [Green Version]
- Weber, J.A.; Baxter, D.H.; Zhang, S.; Huang, D.Y.; Huang, K.H.; Lee, M.J.; Galas, D.J.; Wang, K. The microRNA spectrum in 12 body fluids. Clin. Chem. 2010, 56, 1733–1741. [Google Scholar] [CrossRef]
- Benmoussa, A.; Ly, S.; Shan, S.T.; Laugier, J.; Boilard, E.; Gilbert, C.; Provost, P. A subset of extracellular vesicles carries the bulk of microRNAs in commercial dairy cow’s milk. J. Extracell. Vesicles 2017, 6, 1401897. [Google Scholar] [CrossRef] [Green Version]
- Benmoussa, A.; Laugier, J.; Beauparlant, C.J.; Lambert, M.; Droit, A.; Provost, P. Complexity of the microRNA transcriptome of cow milk and milk-derived extracellular vesicles isolated via differential ultracentrifugation. J. Dairy Sci. 2020, 103, 16–29. [Google Scholar] [CrossRef]
- De la Torre Gomez, C.; Goreham, R.V.; Bech Serra, J.J.; Nann, T.; Kussmann, M. “Exosomics”—A review of biophysics, biology and biochemistry of exosomes with a focus on human breast milk. Front. Genet. 2018, 9, 92. [Google Scholar] [CrossRef] [Green Version]
- Adriano, B.; Cotto, N.M.; Chauhan, N.; Jaggi, M.; Chauhan, S.C.; Yallapu, M.M. Milk exosomes: Nature’s abundant nanoplatform for theranostic applications. Bioact. Mater. 2021, 6, 2479–2490. [Google Scholar] [CrossRef]
- Alsaweed, M.; Lai, C.T.; Hartmann, P.E.; Geddes, D.T.; Kakulas, F. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk. Sci. Rep. 2016, 6, 20680. [Google Scholar] [CrossRef]
- Liao, Y.; Du, X.; Li, J.; Lönnerdal, B. Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol. Nutr. Food Res. 2017, 61, 1700082. [Google Scholar] [CrossRef]
- Kahn, S.; Liao, Y.; Du, X.; Xu, W.; Li, J.; Lönnerdal, B. Exosomal microRNAs in milk from mothers delivering preterm infants survive in vitro digestion and are taken up by human intestinal cells. Mol. Nutr. Food Res. 2018, 62, e1701050. [Google Scholar] [CrossRef]
- Lönnerdal, B. Human milk microRNAs/exosomes: Composition and biological effects. Nestle Nutr. Inst. Workshop Ser. 2019, 90, 83–92. [Google Scholar]
- Sanwlani, R.; Fonseka, P.; Chitti, S.V.; Mathivanan, S. Milk-derived extracellular vesicles in inter-organism, cross-species communication and drug delivery. Proteomes 2020, 8, 11. [Google Scholar] [CrossRef]
- Manca, S.; Upadhyaya, B.; Mutai, E.; Desaulniers, A.T.; Cederberg, R.A.; White, B.R.; Zempleni, J. Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns. Sci. Rep. 2018, 8, 11321. [Google Scholar] [CrossRef] [Green Version]
- Sadri, M.; Shu, J.; Kachman, S.D.; Cui, J.; Zempleni, J. Milk exosomes and miRNA cross the placenta and promote embryo survival in mice. Reproduction 2020, 160, 501–509. [Google Scholar] [CrossRef]
- Golan-Gerstl, R.; Elbaum Shiff, Y.; Moshayoff, V.; Schecter, D.; Leshkowitz, D.; Reif, S. Characterization and biological function of milk-derived miRNAs. Mol. Nutr. Food Res. 2017, 61, 1700009. [Google Scholar] [CrossRef]
- Rubio, M.; Bustamante, M.; Hernandez-Ferrer, C.; Fernandez-Orth, D.; Pantano, L.; Sarria, Y.; Piqué-Borras, M.; Vellve, K.; Agramunt, S.; Carreras, R.; et al. Circulating miRNAs, isomiRs and small RNA clusters in human plasma and breast milk. PLoS ONE 2018, 13, e0193527. [Google Scholar] [CrossRef] [PubMed]
- Smyczynska, U.; Bartlomiejczyk, M.A.; Stanczak, M.M.; Sztromwasser, P.; Wesolowska, A.; Barbarska, O.; Pawlikowska, E.; Fendler, W. Impact of processing method on donated human breast milk microRNA content. PLoS ONE 2020, 15, e0236126. [Google Scholar] [CrossRef] [PubMed]
- Munch, E.M.; Harris, R.A.; Mohammad, M.; Benham, A.L.; Pejerrey, S.M.; Showalter, L.; Hu, M.; Shope, C.D.; Maningat, P.D.; Gunaratne, P.H.; et al. Transcriptome profiling of microRNA by Next-Gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk. PLoS ONE 2013, 8, e50564. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Luo, J.; Sun, S.; Cao, D.; Shi, H.; Loor, J.J. miR-148a and miR-17-5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells. RNA Biol. 2017, 14, 326–338. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Herwijnen, M.J.C.; Driedonks, T.A.P.; Snoek, B.L.; Kroon, A.M.T.; Kleinjan, M.; Jorritsma, R.; Pieterse, C.M.J.; Hoen, E.N.M.N.; Wauben, M.H.M. Abundantly present miRNAs in milk-derived extracellular vesicles are conserved between mammals. Front. Nutr. 2018, 5, 81. [Google Scholar] [CrossRef]
- Chen, Z.; Xie, Y.; Luo, J.; Chen, T.; Xi, Q.; Zhang, Y.; Sun, J. Milk exosome-derived miRNAs from water buffalo are implicated in immune response and metabolism process. BMC Vet. Res. 2020, 16, 123. [Google Scholar] [CrossRef]
- Reif, S.; Elbaum Shiff, Y.; Golan-Gerstl, R. Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner. J. Transl. Med. 2019, 17, 325. [Google Scholar] [CrossRef]
- Pan, W.; Zhu, S.; Yuan, M.; Cui, H.; Wang, L.; Luo, X.; Li, J.; Zhou, H.; Tang, Y.; Shen, N. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J. Immunol. 2010, 184, 6773–6781. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; Schmitz, G. MicroRNAs: Milk’s epigenetic regulators. Best Pract. Res. Clin. Endocrinol. Metab. 2017, 31, 427–442. [Google Scholar] [CrossRef]
- Melnik, B.C.; Schmitz, G. Milk’s role as an epigenetic regulator in health and disease. Diseases 2017, 5, 12. [Google Scholar] [CrossRef]
- Ozkan, H.; Tuzun, F.; Taheri, S.; Korhan, P.; Akokay, P.; Yılmaz, O.; Duman, N.; Özer, E.; Tufan, E.; Kumral, A.; et al. Epigenetic programming through breast milk and its impact on milk-siblings mating. Front. Genet. 2020, 11, 569232. [Google Scholar] [CrossRef]
- Zhou, Q.; Li, M.; Wang, X.; Li, Q.; Wang, T.; Zhu, Q.; Zhou, X.; Wang, X.; Gao, X.; Li, X. Immune-related microRNAs are abundant in breast milk exosomes. Int. J. Biol. Sci. 2012, 8, 118–123. [Google Scholar] [CrossRef]
- Zempleni, J.; Aguilar-Lozano, A.; Sadri, M.; Sukreet, S.; Manca, S.; Wu, D.; Zhou, F.; Mutai, E. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J. Nutr. 2017, 147, 3–10. [Google Scholar] [CrossRef] [Green Version]
- Tomé-Carneiro, J.; Fernández-Alonso, N.; Tomás-Zapico, C.; Visioli, F.; Iglesias-Gutierrez, E.; Dávalos, A. Breast milk microRNAs harsh journey towards potential effects in infant development and maturation. Lipid encapsulation can help. Pharmacol. Res. 2018, 132, 21–32. [Google Scholar] [CrossRef]
- Zempleni, J.; Sukreet, S.; Zhou, F.; Wu, D.; Mutai, E. Milk-derived exosomes and metabolic regulation. Annu. Rev. Anim. Biosci. 2019, 7, 245–262. [Google Scholar] [CrossRef]
- Benmoussa, A.; Provost, P. Milk microRNAs in health and disease. Compr. Rev. Food Sci. Food Saf. 2019, 18, 703–722. [Google Scholar] [CrossRef] [Green Version]
- Galley, J.D.; Besner, G.E. The therapeutic potential of breast milk-derived extracellular vesicles. Nutrients 2020, 12, 745. [Google Scholar]
- Kim, K.U.; Kim, W.H.; Jeong, C.H.; Yi, D.Y.; Min, H. More than nutrition: Therapeutic potential of breast milk-derived exosomes in cancer. Int. J. Mol. Sci. 2020, 21, 7327. [Google Scholar] [CrossRef]
- Carrillo-Lozano, E.; Sebastián-Valles, F.; Knott-Torcal, C. Circulating microRNAs in breast milk and their potential impact on the infant. Nutrients 2020, 12, 3066. [Google Scholar] [CrossRef]
- Kupsco, A.; Prada, D.; Valvi, D.; Hu, L.; Petersen, M.S.; Coull, B.; Grandjean, P.; Weihe, P.; Baccarelli, A.A. Human milk extracellular vesicle miRNA expression and associations with maternal characteristics in a population-based cohort from the Faroe Islands. Sci. Rep. 2021, 11, 5840. [Google Scholar]
- O’Reilly, D.; Dorodnykh, D.; Avdeenko, N.V.; Nekliudov, N.A.; Garssen, J.; Elolimy, A.A.; Petrou, L.; Simpson, M.R.; Yeruva, L.; Munblit, D. Perspective: The role of human breast-milk extracellular vesicles in child health and disease. Adv. Nutr. 2021, 12, 59–70. [Google Scholar] [CrossRef]
- Leiferman, A.; Shu, J.; Upadhyaya, B.; Cui, J.; Zempleni, J. Storage of extracellular vesicles in human milk, and microRNA profiles in human milk exosomes and infant formulas. J. Pediatr. Gastroenterol. Nutr. 2019, 69, 235–238. [Google Scholar] [CrossRef]
- Mulcahy, L.A.; Pink, R.C.; Carter, D.R. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 2014, 3, 24641. [Google Scholar] [CrossRef] [Green Version]
- Abels, E.R.; Breakefield, X.O. Introduction to extracellular vesicles: Biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol. Neurobiol. 2016, 36, 301–312. [Google Scholar] [CrossRef] [PubMed]
- Jadli, A.S.; Ballasy, N.; Edalat, P.; Patel, V.B. Inside(sight) of tiny communicator: Exosome biogenesis, secretion, and uptake. Mol. Cell Biochem. 2020, 467, 77–94. [Google Scholar] [CrossRef] [PubMed]
- Wolf, T.; Baier, S.R.; Zempleni, J. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 Cells. J. Nutr. 2015, 145, 2201–2206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, B.; Hock, A.; Wu, R.Y.; Minich, A.; Botts, S.R.; Lee, C.; Antounians, L.; Miyake, H.; Koike, Y.; Chen, Y.; et al. Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis. PLoS ONE 2019, 14, e0211431. [Google Scholar] [CrossRef] [PubMed]
- Argon, Y.; Bresson, S.E.; Marzec, M.T.; Grimberg, A. Glucose-regulated protein 94 (GRP94): A novel regulator of insulin-like growth factor production. Cells 2020, 9, 1844. [Google Scholar] [CrossRef] [PubMed]
- Ghiasi, S.M.; Dahlby, T.; Hede Andersen, C.; Haataja, L.; Petersen, S.; Omar-Hmeadi, M.; Yang, M.; Pihl, C.; Bresson, S.E.; Khilji, M.S.; et al. Endoplasmic reticulum chaperone glucose-regulated protein 94 is essential for proinsulin handling. Diabetes 2019, 68, 747–760. [Google Scholar] [CrossRef]
- Liu, B.; Staron, M.; Hong, F.; Wu, B.X.; Sun, S.; Morales, C.; Crosson, C.E.; Tomlinson, S.; Kim, I.; Wu, D.; et al. Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway. Proc. Natl. Acad. Sci. USA 2013, 110, 6877–6882. [Google Scholar] [CrossRef] [Green Version]
- Shelby, R.D.; Cromeens, B.; Rager, T.M.; Besner, G.E. Influence of growth factors on the development of necrotizing enterocolitis. Clin. Perinatol. 2019, 46, 51–64. [Google Scholar] [CrossRef]
- Hoeflich, A.; Meyer, Z. Functional analysis of the IGF-system in milk. Best Pract. Res. Clin. Endocrinol. Metab. 2017, 31, 409–418. [Google Scholar] [CrossRef]
- Freier, S.; Eran, M.; Reinus, C.; Ariel, I.; Faber, J.; Wilschanski, M.; Braverman, D. Relative expression and localization of the insulin-like growth factor system components in the fetal, child and adult intestine. J. Pediatr. Gastroenterol. Nutr. 2005, 40, 202–209. [Google Scholar] [CrossRef]
- Chen, T.; Xie, M.Y.; Sun, J.J.; Ye, R.S.; Cheng, X.; Sun, R.P.; Wei, L.M.; Li, M.; Lin, D.L.; Jiang, Q.Y.; et al. Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells. Sci. Rep. 2016, 6, 33862. [Google Scholar] [CrossRef]
- Ozen, S.; Akisu, M.; Baka, M.; Yalaz, M.; Sozmen, E.Y.; Berdeli, A.; Kultursay, N. Insulin-like growth factor attenuates apoptosis and mucosal damage in hypoxia/reoxygenation-induced intestinal injury. Biol. Neonate 2005, 87, 91–96. [Google Scholar] [CrossRef]
- Wilkins, H.R.; Ohneda, K.; Keku, T.O.; D’Ercole, A.J.; Fuller, C.R.; Williams, K.L.; Lund, P.K. Reduction of spontaneous and irradiation-induced apoptosis in small intestine of IGF-I transgenic mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2002, 283, G457–G464. [Google Scholar] [CrossRef] [Green Version]
- Jeschke, M.G.; Bolder, U.; Chung, D.H.; Przkora, R.; Mueller, U.; Thompson, J.C.; Wolf, S.E.; Herndon, D.N. Gut mucosal homeostasis and cellular mediators after severe thermal trauma and the effect of insulin-like growth factor-I in combination with insulin-like growth factor binding protein-3. Endocrinology 2007, 148, 354–362. [Google Scholar] [CrossRef] [Green Version]
- Baregamian, N.; Rychahou, P.G.; Hawkins, H.K.; Evers, B.M.; Chung, D.H. Phosphatidylinositol 3-kinase pathway regulates hypoxia-inducible factor-1 to protect from intestinal injury during necrotizing enterocolitis. Surgery 2007, 142, 295–302. [Google Scholar] [CrossRef] [Green Version]
- Tian, F.; Liu, G.R.; Li, N.; Yuan, G. Insulin-like growth factor I reduces the occurrence of necrotizing enterocolitis by reducing inflammatory response and protecting intestinal mucosal barrier in neonatal rats model. Eur. Rev. Med. Pharmacol. Sci. 2017, 21, 4711–4719. [Google Scholar]
- Ni, F.; Sun, R.; Fu, B.; Wang, F.; Guo, C.; Tian, Z.; Wei, H. IGF-1 promotes the development and cytotoxic activity of human NK cells. Nat. Commun. 2013, 4, 1479. [Google Scholar] [CrossRef]
- Zhang, W.; Frankel, W.L.; Adamson, W.T.; Roth, J.A.; Mantell, M.P.; Bain, A.; Ziegler, T.R.; Smith, R.J.; Rombeau, J.L. Insulin-like growth factor-I improves mucosal structure and function in transplanted rat small intestine. Transplantation 1995, 59, 755–761. [Google Scholar] [CrossRef]
- Lorenzo-Zúñiga, V.; Rodríguez-Ortigosa, C.M.; Bartolí, R.; Martínez-Chantar, M.L.; Martínez-Peralta, L.; Pardo, A.; Ojanguren, I.; Quiroga, J.; Planas, R.; Prieto, J. Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats. Gut 2006, 55, 1306–1312. [Google Scholar] [CrossRef] [Green Version]
- Hunninghake, G.W.; Doerschug, K.C.; Nymon, A.B.; Schmidt, G.A.; Meyerholz, D.K.; Ashare, A. Insulin-like growth factor-1 levels contribute to the development of bacterial translocation in sepsis. Am. J. Respir. Crit. Care Med. 2010, 182, 517–525. [Google Scholar] [CrossRef]
- Corpeleijn, W.E.; van Vliet, I.; de Gast-Bakker, D.A.; van der Schoor, S.R.; Alles, M.S.; Hoijer, M.; Tibboel, D.; van Goudoever, J.B. Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates. J. Pediatr. Gastroenterol. Nutr. 2008, 46, 184–190. [Google Scholar] [CrossRef]
- Rowland, K.J.; Choi, P.M.; Warner, B.W. The role of growth factors in intestinal regeneration and repair in necrotizing enterocolitis. Semin. Pediatr. Surg. 2013, 22, 101–111. [Google Scholar] [CrossRef] [Green Version]
- Ouni, M.; Gunes, Y.; Belot, M.P.; Castell, A.L.; Fradin, D.; Bougnères, P. The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth. Clin. Epigenetics 2015, 7, 22. [Google Scholar]
- Ouni, M.; Castell, A.L.; Linglart, A.; Bougnères, P. Genetic and epigenetic modulation of growth hormone sensitivity studied with the IGF-1 generation test. J. Clin. Endocrinol. Metab. 2015, 100, E919–E925. [Google Scholar] [CrossRef] [Green Version]
- Ouni, M.; Belot, M.P.; Castell, A.L.; Fradin, D.; Bougnères, P. The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness. Pharmacogenomics J. 2016, 16, 102–106. [Google Scholar] [CrossRef] [Green Version]
- Ma, M.; Zhou, Q.J.; Xiong, Y.; Li, B.; Li, X.T. Preeclampsia is associated with hypermethylation of IGF-1 promoter mediated by DNMT1. Am. J. Transl. Res. 2018, 10, 16–39. [Google Scholar] [PubMed]
- Yu, S.; Zhao, Z.; Sun, L.; Li, P. Fermentation results in quantitative changes in milk-derived exosomes and different effects on cell growth and survival. J. Agric. Food Chem. 2017, 65, 1220–1228. [Google Scholar] [CrossRef] [PubMed]
- Hock, A.; Miyake, H.; Li, B.; Lee, C.; Ermini, L.; Koike, Y.; Chen, Y.; Määttänen, P.; Zani, A.; Pierro, A. Breast milk-derived exosomes promote intestinal epithelial cell growth. J. Pediatr. Surg. 2017, 52, 755–759. [Google Scholar] [CrossRef] [PubMed]
- Gao, H.N.; Guo, H.Y.; Zhang, H.; Xie, X.L.; Wen, P.C.; Ren, F.Z. Yak-milk-derived exosomes promote proliferation of intestinal epithelial cells in an hypoxic environment. J. Dairy Sci. 2019, 102, 985–996. [Google Scholar] [CrossRef] [Green Version]
- Gao, H.N.; Ren, F.Z.; Wen, P.C.; Xie, L.X.; Wang, R.; Yang, Z.N.; Li, Y.X. Yak milk-derived exosomal microRNAs regulate intestinal epithelial cells on proliferation in hypoxic environment. J. Dairy Sci. 2021, 104, 1291–1303. [Google Scholar] [CrossRef] [PubMed]
- Ross, M.; Atalla, H.; Karrow, N.; Mallard, B.A. The bioactivity of colostrum and milk exosomes of high, average, and low immune responder cows on human intestinal epithelial cells. J. Dairy Sci. 2021, 104, 2499–2510. [Google Scholar] [CrossRef]
- Barker, N.; van Es, J.H.; Kuipers, J.; Kujala, P.; van den Born, M.; Cozijnsen, M.; Haegebarth, A.; Korving, J.; Begthel, H.; Peters, P.J.; et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007, 449, 1003–1007. [Google Scholar] [CrossRef]
- Fernandez Vallone, V.; Leprovots, M.; Ribatallada-Soriano, D.; Gerbier, R.; Lefort, A.; Libert, F.; Vassart, G.; Garcia, M.I. LGR5 controls extracellular matrix production by stem cells in the developing intestine. EMBO Rep. 2020, 21, e49224. [Google Scholar] [CrossRef]
- Dong, P.; Zhang, Y.; Yan, D.Y.; Wang, Y.; Xu, X.; Zhao, Y.C.; Xiao, T.T. Protective effects of human milk-derived exosomes on intestinal stem cells damaged by oxidative stress. Cell Transplant. 2020, 29, 963689720912690. [Google Scholar] [CrossRef] [Green Version]
- Buckley, A.; Turner, J.R. Cell biology of tight junction barrier regulation and mucosal disease. Cold Spring Harb. Perspect. Biol. 2018, 10, a029314. [Google Scholar] [CrossRef]
- Ravisankar, S.; Tatum, R.; Garg, P.M.; Herco, M.; Shekhawat, P.S.; Chen, Y.H. Necrotizing enterocolitis leads to disruption of tight junctions and increase in gut permeability in a mouse model. BMC Pediatr. 2018, 18, 372. [Google Scholar] [CrossRef]
- Liu, D.; Xu, Y.; Feng, J.; Yu, J.; Huang, J.; Li, Z. Mucins and tight junctions are severely altered in necrotizing enterocolitis neonates. Am. J. Perinatol. 2020. [Google Scholar] [CrossRef]
- Camilleri, M.; Madsen, K.; Spiller, R.; Greenwood-Van Meerveld, B.; Verne, G.N. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol. Motil. 2012, 24, 503–512. [Google Scholar] [CrossRef]
- Furuse, M.; Hata, M.; Furuse, K.; Yoshida, Y.; Haratake, A.; Sugitani, Y.; Noda, T.; Kubo, A.; Tsukita, S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice. J. Cell Biol. 2002, 156, 1099–1111. [Google Scholar] [CrossRef]
- Fanning, A.S.; Jameson, B.J.; Jesaitis, L.A.; Anderson, J.M. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J. Biol. Chem. 1998, 273, 29745–29753. [Google Scholar] [CrossRef] [Green Version]
- Benmoussa, A.; Diallo, I.; Salem, M.; Michel, S.; Gilbert, C.; Sévigny, J.; Provost, P. Concentrates of two subsets of extracellular vesicles from cow’s milk modulate symptoms and inflammation in experimental colitis. Sci. Rep. 2019, 9, 14661. [Google Scholar] [CrossRef] [Green Version]
- Xie, M.Y.; Chen, T.; Xi, Q.Y.; Hou, L.J.; Luo, J.Y.; Zeng, B.; Li, M.; Sun, J.J.; Zhang, L. Porcine milk exosome miRNAs protect intestinal epithelial cells against deoxynivalenol-induced damage. Biochem. Pharmacol. 2020, 175, 113898. [Google Scholar] [CrossRef]
- He, S.; Liu, G.; Zhu, X. Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity. Pediatr. Res. 2021. [Google Scholar] [CrossRef]
- Cornick, S.; Tawiah, A.; Chadee, K. Roles and regulation of the mucus barrier in the gut. Tissue Barriers 2015, 3, e982426. [Google Scholar] [CrossRef] [Green Version]
- Paone, P.; Cani, P.D. Mucus barrier, mucins and gut microbiota: The expected slimy partners? Gut 2020, 69, 2232–2243. [Google Scholar] [CrossRef]
- Forstner, G. Signal transduction, packaging and secretion of mucins. Annu. Rev. Physiol. 1995, 57, 585–605. [Google Scholar] [CrossRef] [PubMed]
- Johansson, M.E.; Hansson, G.C. Immunological aspects of intestinal mucus and mucins. Nat. Rev. Immunol. 2016, 16, 639–649. [Google Scholar] [CrossRef] [PubMed]
- Tong, L.; Hao, H.; Zhang, X.; Zhang, Z.; Lv, Y.; Zhang, L.; Yi, H. Oral administration of bovine milk-derived extracellular vesicles alters the gut microbiota and enhances intestinal immunity in mice. Mol. Nutr. Food Res. 2020, 64, e1901251. [Google Scholar] [CrossRef] [PubMed]
- Miyake, H.; Lee, C.; Chusilp, S.; Bhalla, M.; Li, B.; Pitino, M.; Seo, S.; O’Connor, D.L.; Pierro, A. Human breast milk exosomes attenuate intestinal damage. Pediatr. Surg. Int. 2020, 36, 155–163. [Google Scholar] [CrossRef] [PubMed]
- Camilleri, M. Leaky gut: Mechanisms, measurement and clinical implications in humans. Gut 2019, 68, 1516–1526. [Google Scholar] [CrossRef] [PubMed]
- Hansson, G.C. Mucins and the microbiome. Annu. Rev. Biochem. 2020, 89, 769–793. [Google Scholar] [CrossRef] [Green Version]
- Johansson, M.E.V.; Sjövall, H.; Hansson, G.C. The gastrointestinal mucus system in health and disease. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 352–361. [Google Scholar] [CrossRef] [Green Version]
- Pelaseyed, T.; Bergström, J.H.; Gustafsson, J.K.; Ermund, A.; Birchenough, G.M.; Schütte, A.; van der Post, S.; Svensson, F.; Rodríguez-Piñeiro, A.M.; Nyström, E.E.; et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol. Rev. 2014, 260, 8–20. [Google Scholar] [CrossRef] [Green Version]
- Schroeder, B.O. Fight them or feed them: How the intestinal mucus layer manages the gut microbiota. Gastroenterol. Rep. 2019, 7, 3–12. [Google Scholar] [CrossRef] [Green Version]
- Vaishnava, S.; Yamamoto, M.; Severson, K.M.; Ruhn, K.A.; Yu, X.; Koren, O.; Ley, R.; Wakeland, E.K.; Hooper, L.V. The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science 2011, 334, 255–258. [Google Scholar] [CrossRef] [Green Version]
- Santaolalla, R.; Abreu, M.T. Innate immunity in the small intestine. Curr. Opin. Gastroenterol. 2012, 28, 124–129. [Google Scholar] [CrossRef] [Green Version]
- Friedrich, C.; Mamareli, P.; Thiemann, S.; Kruse, F.; Wang, Z.; Holzmann, B.; Strowig, T.; Sparwasser, T.; Lochner, M. MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium. PLoS Pathog. 2017, 13, e1006357. [Google Scholar] [CrossRef] [Green Version]
- Ronellenfitsch, S.; Weiß, C.; Frommhold, D.; Koch, L.; Mollenhauer, J.; Poeschl, J.; Müller, H. High DMBT1 concentrations in breast milk correlate with increased risk of infection in preterm and term neonates. BMC Pediatr. 2012, 12, 157. [Google Scholar] [CrossRef] [Green Version]
- Chen, C.Y.; Rao, S.S.; Ren, L.; Hu, X.K.; Tan, Y.J.; Hu, Y.; Luo, J.; Liu, Y.W.; Yin, H.; Huang, J.; et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics 2018, 8, 1607–1623. [Google Scholar] [CrossRef]
- Yu, S.; Zhao, Z.; Xu, X.; Li, M.; Li, P. Characterization of three different types of extracellular vesicles and their impact on bacterial growth. Food Chem. 2019, 272, 372–378. [Google Scholar] [CrossRef]
- Zhou, F.; Paz, H.A.; Sadri, M.; Cui, J.; Kachman, S.D.; Fernando, S.C.; Zempleni, J. Dietary bovine milk exosomes elicit changes in bacterial communities in C57BL/6 mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2019, 317, G618–G624. [Google Scholar] [CrossRef]
- Zhang, J.; Song, L.; Wang, Y.; Liu, C.; Zhang, L.; Zhu, S.; Liu, S.; Duan, L. Beneficial effect of butyrate-producing Lachnospiraceae on stress-induced visceral hypersensitivity in rats. J. Gastroenterol. Hepatol. 2019, 34, 1368–1376. [Google Scholar] [CrossRef] [Green Version]
- Sasaki, K.; Inoue, J.; Sasaki, D.; Hoshi, N.; Shirai, T.; Fukuda, I.; Azuma, T.; Kondo, A.; Osawa, R. Construction of a model culture system of human colonic microbiota to detect decreased Lachnospiraceae abundance and butyrogenesis in the feces of ulcerative colitis patients. Biotechnol. J. 2019, 14, e1800555. [Google Scholar] [CrossRef]
- Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504, 451–455. [Google Scholar] [CrossRef]
- Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013, 504, 446–450. [Google Scholar] [CrossRef]
- Ruohtula, T.; de Goffau, M.C.; Nieminen, J.K.; Honkanen, J.; Siljander, H.; Hämäläinen, A.M.; Peet, A.; Tillmann, V.; Ilonen, J.; Niemelä, O.; et al. Maturation of gut microbiota and circulating regulatory T cells and development of IgE sensitization in early life. Front. Immunol. 2019, 10, 2494. [Google Scholar] [CrossRef]
- Feuerer, M.; Hill, J.A.; Mathis, D.; Benoist, C. Foxp3+ regulatory T cells:differentiation, specification, subphenotypes. Nat. Immunol. 2009, 10, 689–695. [Google Scholar] [CrossRef]
- Yamashiro, Y. Gut microbiota in health and disease. Ann. Nutr. Metab. 2017, 71, 242–246. [Google Scholar] [CrossRef]
- Figliuolo da Paz, V.R.; Jamwal, D.R.; Kiela, P.R. Intestinal regulatory T cells. Adv. Exp. Med. Biol. 2021, 1278, 141–190. [Google Scholar] [PubMed]
- Weitkamp, J.H.; Rudzinski, E.; Koyama, T.; Correa, H.; Matta, P.; Alberty, B.; Polk, D.B. Ontogeny of FOXP3(+) regulatory T cells in the postnatal human small intestinal and large intestinal lamina propria. Pediatr. Dev. Pathol. 2009, 12, 443–449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tanoue, T.; Atarashi, K.; Honda, K. Development and maintenance of intestinal regulatory T cells. Nat. Rev. Immunol. 2016, 16, 295–309. [Google Scholar] [CrossRef]
- Hadis, U.; Wahl, B.; Schulz, O.; Hardtke-Wolenski, M.; Schippers, A.; Wagner, N.; Müller, W.; Sparwasser, T.; Förster, R.; Pabst, O. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 2011, 34, 237–246. [Google Scholar] [CrossRef]
- Tordesillas, L.; Berin, M.C. Mechanisms of oral tolerance. Clin. Rev. Allergy Immunol. 2018, 55, 107–117. [Google Scholar] [CrossRef] [PubMed]
- Huehn, J.; Beyer, M. Epigenetic and transcriptional control of Foxp3+ regulatory T cells. Semin. Immunol. 2015, 27, 10–18. [Google Scholar] [CrossRef]
- Bellanti, J.A.; Li, D. Treg cells and epigenetic regulation. Adv. Exp. Med. Biol. 2021, 1278, 95–114. [Google Scholar]
- Polansky, J.K.; Kretschmer, K.; Freyer, J.; Floess, S.; Garbe, A.; Baron, U.; Olek, S.; Hamann, A.; von Boehmer, H.; Huehn, J. DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 2008, 38, 1654–1663. [Google Scholar] [CrossRef]
- Toker, A.; Engelbert, D.; Garg, G.; Polansky, J.K.; Floess, S.; Miyao, T.; Baron, U.; Düber, S.; Geffers, R.; Giehr, P.; et al. Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J. Immunol. 2013, 190, 3180–3188. [Google Scholar] [CrossRef] [Green Version]
- Schreiber, L.; Pietzsch, B.; Floess, S.; Farah, C.; Jänsch, L.; Schmitz, I.; Huehn, J. The Treg-specific demethylated region stabilizes Foxp3 expression independently of NF-κB signaling. PLoS ONE 2014, 9, e88318. [Google Scholar] [CrossRef]
- Lal, G.; Bromberg, J.S. Epigenetic mechanisms of regulation of Foxp3 expression. Blood 2009, 114, 3727–3735. [Google Scholar] [CrossRef] [Green Version]
- Lal, G.; Zhang, N.; van der Touw, W.; Ding, Y.; Ju, W.; Bottinger, E.P.; Reid, S.P.; Levy, D.E.; Bromberg, J.S. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 2009, 182, 259–273. [Google Scholar] [CrossRef]
- Melnik, B.C.; John, S.M.; Schmitz, G. Milk: An exosomal microRNA transmitter promoting thymic regulatory T cell maturation preventing the development of atopy? J. Transl. Med. 2014, 12, 43. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; John, S.M.; Carrera-Bastos, P.; Schmitz, G. Milk: A postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. Clin. Transl. Allergy 2016, 6, 18. [Google Scholar] [CrossRef] [Green Version]
- Robbins, P.D.; Morelli, A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014, 14, 195–208. [Google Scholar] [CrossRef] [Green Version]
- Seo, N. Exosome-mediated immune regulation and its clinical application. Trends Immunother. 2020, 4, 36–41. [Google Scholar] [CrossRef]
- Wani, S.; Man Law, I.K.; Pothoulakis, C. Role and mechanisms of exosomal miRNAs in IBD pathophysiology. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 319, G646–G654. [Google Scholar] [CrossRef]
- Ocansey, D.K.W.; Zhang, L.; Wang, Y.; Yan, Y.; Qian, H.; Zhang, X.; Xu, W.; Mao, F. Exosome-mediated effects and applications in inflammatory bowel disease. Biol. Rev. Camb. Philos. Soc. 2020, 95, 1287–1307. [Google Scholar] [CrossRef]
- Admyre, C.; Johansson, S.M.; Qazi, K.R.; Filén, J.J.; Lahesmaa, R.; Norman, M.; Neve, E.P.; Scheynius, A.; Gabrielsson, S. Exosomes with immune modulatory features are present in human breast milk. J. Immunol. 2007, 179, 1969–1978. [Google Scholar] [CrossRef]
- Tooley, K.L.; El-Merhibi, A.; Cummins, A.G.; Grose, R.H.; Lymn, K.A.; DeNichilo, M.; Penttila, I.A. Maternal milk, but not formula, regulates the immune response to beta-lactoglobulin in allergy-prone rat pups. J. Nutr. 2009, 139, 2145–2151. [Google Scholar] [CrossRef]
- Paparo, L.; Nocerino, R.; Cosenza, L.; Aitoro, R.; D’Argenio, V.; Del Monaco, V.; Di Scala, C.; Amoroso, A.; Di Costanzo, M.; Salvatore, F.; et al. Epigenetic features of FoxP3 in children with cow’s milk allergy. Clin. Epigenetics 2016, 8, 86. [Google Scholar] [CrossRef] [Green Version]
- Kanjarawi, R.; Dercamp, C.; Etchart, N.; Adel-Patient, K.; Nicolas, J.F.; Dubois, B.; Kaiserlian, D. Regulatory T cells control type I food allergy to beta-lactoglobulin in mice. Int. Arch. Allergy Immunol. 2011, 156, 387–396. [Google Scholar] [CrossRef]
- Wang, M.; Yang, I.V.; Davidson, E.J.; Joetham, A.; Takeda, K.; O’Connor, B.P.; Gelfand, E.W. Forkhead box protein 3 demethylation is associated with tolerance induction in peanut-induced intestinal allergy. J. Allergy Clin. Immunol. 2018, 141, 659–670. [Google Scholar] [CrossRef] [Green Version]
- Okoye, I.S.; Coomes, S.M.; Pelly, V.S.; Czieso, S.; Papayannopoulos, V.; Tolmachova, T.; Seabra, M.C.; Wilson, M.S. MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 2014, 41, 89–103. [Google Scholar] [CrossRef] [Green Version]
- Lluis, A.; Depner, M.; Gaugler, B.; Saas, P.; Casaca, V.I.; Raedler, D.; Michel, S.; Tost, J.; Liu, J.; Genuneit, J.; et al. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood. J. Allergy Clin. Immunol. 2014, 133, 551–559. [Google Scholar]
- Loss, G.; Apprich, S.; Waser, M.; Kneifel, W.; Genuneit, J.; Büchele, G.; Weber, J.; Sozanska, B.; Danielewicz, H.; Horak, E.; et al. The protective effect of farm milk consumption on childhood asthma and atopy: The GABRIELA study. J. Allergy Clin. Immunol. 2011, 128, 766–773. [Google Scholar] [CrossRef]
- Brick, T.; Hettinga, K.; Kirchner, B.; Pfaffl, M.W.; Ege, M.J. The beneficial effect of farm milk consumption on asthma, allergies, and infections: From meta-analysis of evidence to clinical trial. J. Allergy Clin. Immunol. Pract. 2020, 8, 878–889. [Google Scholar] [CrossRef]
- Kirchner, B.; Pfaffl, M.W.; Dumpler, J.; von Mutius, E.; Ege, M.J. microRNA in native and processed cow’s milk and its implication for the farm milk effect on asthma. J. Allergy Clin. Immunol. 2016, 137, 1893–1895. [Google Scholar] [CrossRef] [Green Version]
- Kleinjan, M.; van Herwijnen, M.J.; Libregts, S.F.; van Neerven, R.J.; Feitsma, A.L.; Wauben, M.H. Regular industrial processing of bovine milk impacts the integrity and molecular composition of extracellular vesicles. J. Nutr. 2021. [Google Scholar] [CrossRef]
- Sozańska, B.; Pearce, N.; Dudek, K.; Cullinan, P. Consumption of unpasteurized milk and its effects on atopy and asthma in children and adult inhabitants in rural Poland. Allergy 2013, 68, 644–650. [Google Scholar] [CrossRef] [PubMed]
- Ismail, R.I.H.; Awad, H.A.; Imam, S.S.; Gad, G.I.; Aboushady, N.M.; Abdou, R.M.; Eissa, D.S.; Azzam, N.T.; Barakat, M.M.; Yassin, M.M.; et al. Gut priming with bovine colostrum and T regulatory cells in preterm neonates: A randomized controlled trial. Pediatr. Res. 2021. [Google Scholar] [CrossRef] [PubMed]
- Zheng, S.G.; Gray, J.D.; Ohtsuka, K.; Yamagiwa, S.; Horwitz, D.A. Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors. J. Immunol. 2002, 169, 4183–4189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zheng, S.G.; Wang, J.H.; Gray, J.D.; Soucier, H.; Horwitz, D.A. Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: The role of IL-2, TGF-beta, and IL-10. J. Immunol. 2004, 172, 5213–5221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kanamori, M.; Nakatsukasa, H.; Okada, M.; Lu, Q.; Yoshimura, A. Induced regulatory T cells: Their development, stability, and applications. Trends Immunol. 2016, 37, 803–811. [Google Scholar] [CrossRef]
- Li, C.; Ebert, P.J.; Li, Q.J. T cell receptor (TCR) and transforming growth factor β (TGF-β) signaling converge on DNA (cytosine-5)-methyltransferase to control forkhead box protein 3 (foxp3) locus methylation and inducible regulatory T cell differentiation. J. Biol. Chem. 2013, 288, 19127–19139. [Google Scholar] [CrossRef] [Green Version]
- Pieters, B.C.; Arntz, O.J.; Bennink, M.B.; Broeren, M.G.; van Caam, A.P.; Koenders, M.I.; van Lent, P.L.; van den Berg, W.B.; de Vries, M.; van der Kraan, P.M.; et al. Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β. PLoS ONE 2015, 10, e0121123. [Google Scholar] [CrossRef]
- Reif, S.; Elbaum-Shiff, Y.; Koroukhov, N.; Shilo, I.; Musseri, M.; Golan-Gerstl, R. Cow and human milk-derived exosomes ameliorate colitis in DSS murine model. Nutrients 2020, 12, 2589. [Google Scholar] [CrossRef]
- Qin, W.; Tsukasaki, Y.; Dasgupta, S.; Mukhopadhyay, N.; Ikebe, M.; Sauter, E.R. Exosomes in human breast milk promote EMT. Clin. Cancer Res. 2016, 22, 4517–4524. [Google Scholar] [CrossRef] [Green Version]
- Kalliomäki, M.; Ouwehand, A.; Arvilommi, H.; Kero, P.; Isolauri, E. Transforming growth factor-beta in breast milk: A potential regulator of atopic disease at an early age. J. Allergy Clin. Immunol. 1999, 104, 1251–1257. [Google Scholar] [CrossRef]
- Rigotti, E.; Piacentini, G.L.; Ress, M.; Pigozzi, R.; Boner, A.L.; Peroni, D.G. Transforming growth factor-beta and interleukin-10 in breast milk and development of atopic diseases in infants. Clin. Exp. Allergy 2006, 36, 614–618. [Google Scholar] [CrossRef]
- Kohlhaas, S.; Garden, O.A.; Scudamore, C.; Turner, M.; Okkenhaug, K.; Vigorito, E. Cutting edge: The Foxp3 target miR-155 contributes to the development of regulatory T cells. J. Immunol. 2009, 182, 2578–2582. [Google Scholar] [CrossRef]
- Yao, R.; Ma, Y.L.; Liang, W.; Li, H.H.; Ma, Z.J.; Yu, X.; Liao, Y.H. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 2012, 7, e46082. [Google Scholar] [CrossRef] [Green Version]
- Na, R.S.; E, G.X.; Sun, W.; Sun, X.W.; Qiu, X.Y.; Chen, L.P.; Huang, Y.F. Expressional analysis of immune-related miRNAs in breast milk. Genet. Mol. Res. 2015, 14, 11371–11376. [Google Scholar] [CrossRef]
- Izumi, H.; Kosaka, N.; Shimizu, T.; Sekine, K.; Ochiya, T.; Takase, M. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J. Dairy Sci. 2012, 95, 4831–4841. [Google Scholar] [CrossRef] [Green Version]
- Lu, L.F.; Thai, T.H.; Calado, D.P.; Chaudhry, A.; Kubo, M.; Tanaka, K.; Loeb, G.B.; Lee, H.; Yoshimura, A.; Rajewsky, K.; et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 2009, 30, 80–91. [Google Scholar] [CrossRef] [Green Version]
- Zeng, Q.; Liu, W.; Luo, R.; Lu, G. MicroRNA-181a and microRNA-155 are involved in the regulation of the differentiation and function of regulatory T cells in allergic rhinitis children. Pediatr. Allergy Immunol. 2019, 30, 434–442. [Google Scholar] [CrossRef]
- Li, D.P.; Fan, J.; Wu, Y.J.; Xie, Y.F.; Zha, J.M.; Zhou, X.M. MiR-155 up-regulated by TGF-β promotes epithelial-mesenchymal transition, invasion and metastasis of human hepatocellular carcinoma cells in vitro. Am. J. Transl. Res. 2017, 9, 2956–2965. [Google Scholar]
- Elton, T.S.; Selemon, H.; Elton, S.M.; Parinandi, N.L. Regulation of the MIR155 host gene in physiological and pathological processes. Gene 2013, 532, 1–12. [Google Scholar] [CrossRef]
- O’Connor, E.B.; Muñoz-Wolf, N.; Leon, G.; Lavelle, E.C.; Mills, K.H.G.; Walsh, P.T.; Porter, R.K. UCP3 reciprocally controls CD4+ Th17 and Treg cell differentiation. PLoS ONE 2020, 15, e0239713. [Google Scholar] [CrossRef]
- Arntz, O.J.; Pieters, B.C.; Oliveira, M.C.; Broeren, M.G.; Bennink, M.B.; de Vries, M.; van Lent, P.L.; Koenders, M.I.; van den Berg, W.B.; van der Kraan, P.M.; et al. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Mol. Nutr. Food Res. 2015, 59, 1701–1712. [Google Scholar] [CrossRef] [PubMed]
- Xie, M.Y.; Hou, L.J.; Sun, J.J.; Zeng, B.; Xi, Q.Y.; Luo, J.Y.; Chen, T.; Zhang, Y.L. Porcine milk exosome miRNAs attenuate LPS-induced apoptosis through inhibiting TLR4/NF-κB and p53 pathways in intestinal epithelial cells. J. Agric. Food Chem. 2019, 67, 9477–9491. [Google Scholar] [CrossRef] [PubMed]
- Gao, R.; Zhang, R.; Qian, T.; Peng, X.; He, W.; Zheng, S.; Cao, Y.; Pierro, A.; Shen, C. A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury. Pediatr. Surg. Int. 2019, 35, 1363–1368. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Gao, C.; Li, H.; Huang, L.; Sun, Q.; Dong, Y.; Tian, C.; Gao, S.; Dong, H.; Guan, D.; et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res. 2010, 20, 1128–1137. [Google Scholar] [CrossRef]
- Taganov, K.D.; Boldin, M.P.; Chang, K.J.; Baltimore, D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl. Acad. Sci. USA 2006, 103, 12481–12486. [Google Scholar] [CrossRef] [Green Version]
- Hou, J.; Wang, P.; Lin, L.; Liu, X.; Ma, F.; An, H.; Wang, Z.; Cao, X. MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J. Immunol. 2009, 183, 2150–2158. [Google Scholar] [CrossRef] [Green Version]
- O’Connell, R.M.; Taganov, K.D.; Boldin, M.P.; Cheng, G.; Baltimore, D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. USA 2007, 104, 1604–1609. [Google Scholar] [CrossRef] [Green Version]
- Tili, E.; Michaille, J.J.; Cimino, A.; Costinean, S.; Dumitru, C.D.; Adair, B.; Fabbri, M.; Alder, H.; Liu, C.G.; Calin, G.A.; et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J. Immunol. 2007, 179, 5082–5089. [Google Scholar] [CrossRef]
- Sheedy, F.J.; Palsson-McDermott, E.; Hennessy, E.J.; Martin, C.; O’Leary, J.J.; Ruan, Q.; Johnson, D.S.; Chen, Y.; O’Neill, L.A. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat. Immunol. 2010, 11, 141–147. [Google Scholar] [CrossRef]
- Herrmann, T.L.; Morita, C.T.; Lee, K.; Kusner, D.J. Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells. J. Leukoc. Biol. 2005, 78, 1397–1407. [Google Scholar] [CrossRef] [Green Version]
- Turner, M.L.; Schnorfeil, F.M.; Brocker, T. MicroRNAs regulate dendritic cell differentiation and function. J. Immunol. 2011, 187, 3911–3917. [Google Scholar] [CrossRef]
- Liu, X.; Zhan, Z.; Xu, L.; Ma, F.; Li, D.; Guo, Z.; Li, N.; Cao, X. MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. J. Immunol. 2010, 185, 7244–7251. [Google Scholar] [CrossRef]
- Herrmann, T.L.; Agrawal, R.S.; Connolly, S.F.; McCaffrey, R.L.; Schlomann, J.; Kusner, D.J. MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II. J. Leukoc. Biol. 2007, 82, 686–699. [Google Scholar] [CrossRef]
- Hughes, K.; Edin, S.; Antonsson, A.; Grundström, T. Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkappaB kinase. J. Biol. Chem. 2001, 276, 36008–36013. [Google Scholar] [CrossRef] [Green Version]
- Ishiguro, K.; Green, T.; Rapley, J.; Wachtel, H.; Giallourakis, C.; Landry, A.; Cao, Z.; Lu, N.; Takafumi, A.; Goto, H.; et al. Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF-kappaB activation. Mol. Cell. Biol. 2006, 26, 5497–5508. [Google Scholar] [CrossRef] [Green Version]
- Patel, V.; Carrion, K.; Hollands, A.; Hinton, A.; Gallegos, T.; Dyo, J.; Sasik, R.; Leire, E.; Hardiman, G.; Mohamed, S.A.; et al. The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells. FASEB J. 2015, 29, 1859–1868. [Google Scholar] [CrossRef] [Green Version]
- Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol. 2009, 1, a001651. [Google Scholar] [CrossRef] [Green Version]
- Wullaert, A.; Bonnet, M.C.; Pasparakis, M. NF-κB in the regulation of epithelial homeostasis and inflammation. Cell Res. 2011, 21, 146–158. [Google Scholar] [CrossRef]
- Bettelli, E.; Dastrange, M.; Oukka, M. Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl. Acad. Sci. USA 2005, 102, 5138–5143. [Google Scholar] [CrossRef] [Green Version]
- Kim, C.H. FOXP3 and its role in the immune system. Adv. Exp. Med. Biol. 2009, 665, 17–29. [Google Scholar]
- Auphan, N.; DiDonato, J.A.; Rosette, C.; Helmberg, A.; Karin, M. Immunosuppression by glucocorticoids: Inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 1995, 270, 286–290. [Google Scholar] [CrossRef]
- Scheinman, R.I.; Cogswell, P.C.; Lofquist, A.K.; Baldwin, A.S., Jr. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science 1995, 270, 283–286. [Google Scholar] [CrossRef] [Green Version]
- Almawi, W.Y.; Melemedjian, O.K. Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids. J. Mol. Endocrinol. 2002, 28, 69–78. [Google Scholar] [CrossRef] [Green Version]
- Carney, M.C.; Tarasiuk, A.; DiAngelo, S.L.; Silveyra, P.; Podany, A.; Birch, L.L.; Paul, I.M.; Kelleher, S.; Hicks, S.D. Metabolism-related microRNAs in maternal breast milk are influenced by premature delivery. Pediatr. Res. 2017, 82, 226–236. [Google Scholar] [CrossRef]
- Huang, Z.P.; Wang, D.Z. miR-22 in cardiac remodeling and disease. Trends Cardiovasc. Med. 2014, 24, 267–272. [Google Scholar] [CrossRef] [Green Version]
- Diniz, G.P.; Huang, Z.P.; Liu, J.; Chen, J.; Ding, J.; Fonseca, R.I.; Barreto-Chaves, M.L.; Donato, J., Jr.; Hu, X.; Wang, D.Z. Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy. Clin. Sci. 2017, 131, 2885–2900. [Google Scholar] [CrossRef]
- Yang, Z.; Qin, W.; Huo, J.; Zhuo, Q.; Wang, J.; Wang, L. MiR-22 modulates the expression of lipogenesis-related genes and promotes hepatic steatosis in vitro. FEBS Open Bio 2021, 11, 322–332. [Google Scholar] [CrossRef]
- Thibonnier, M.; Esau, C.; Ghosh, S.; Wargent, E.; Stocker, C. Metabolic and energetic benefits of microRNA-22 inhibition. BMJ Open Diabetes Res. Care 2020, 8, e001478. [Google Scholar] [CrossRef] [PubMed]
- Lin, J.; Huo, R.; Xiao, L.; Zhu, X.; Xie, J.; Sun, S.; He, Y.; Zhang, J.; Sun, Y.; Zhou, Z.; et al. A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014, 66, 49–59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Emre, Y.; Imhof, B.A. Matricellular protein CCN1/CYR61: A new player in inflammation and leukocyte trafficking. Semin. Immunopathol. 2014, 36, 253–259. [Google Scholar] [CrossRef] [PubMed]
- Hu, T.; Chen, B.; Zhou, S.; Mao, J. Simvastatin inhibits inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through the microRNA-22/Cyr61 axis. Int. J. Clin. Exp. Pathol. 2018, 11, 3925–3933. [Google Scholar]
- Shegarfi, H.; Krohn, C.D.; Gundersen, Y.; Kjeldsen, S.F.; Hviid, C.V.; Ruud, T.E.; Aasen, A.O. Regulation of CCN1 (Cyr61) in a porcine model of intestinal ischemia/reperfusion. Innate Immun. 2015, 21, 453–462. [Google Scholar] [CrossRef]
- Yang, J.; Fan, Z.; Yang, J.; Ding, J.; Yang, C.; Chen, L. microRNA-22 attenuates myocardial ischemia-reperfusion injury via an anti-inflammatory mechanism in rats. Exp. Ther. Med. 2016, 12, 3249–3255. [Google Scholar] [CrossRef] [Green Version]
- Yang, J.; Chen, L.; Yang, J.; Ding, J.; Li, S.; Wu, H.; Zhang, J.; Fan, Z.; Dong, W.; Li, X. MicroRNA-22 targeting CBP protects against myocardial ischemia-reperfusion injury through anti-apoptosis in rats. Mol. Biol. Rep. 2014, 41, 555–561. [Google Scholar] [CrossRef]
- Bai, T.; Chen, C.C.; Lau, L.F. Matricellular protein CCN1 activates a proinflammatory genetic program in murine macrophages. J. Immunol. 2010, 184, 3223–3232. [Google Scholar] [CrossRef] [Green Version]
- Yu, H.; Wu, M.; Zhao, P.; Huang, Y.; Wang, W.; Yin, W. Neuroprotective effects of viral overexpression of microRNA-22 in rat and cell models of cerebral ischemia-reperfusion injury. J. Cell Biochem. 2015, 116, 233–241. [Google Scholar] [CrossRef]
- Takata, A.; Otsuka, M.; Kojima, K.; Yoshikawa, T.; Kishikawa, T.; Yoshida, H.; Koike, K. MicroRNA-22 and microRNA-140 suppress NF-κB activity by regulating the expression of NF-κB coactivators. Biochem. Biophys. Res. Commun. 2011, 411, 826–831. [Google Scholar] [CrossRef]
- Liang, X.; Liu, Y.; Mei, S.; Zhang, M.; Xin, J.; Zhang, Y.; Yang, R. MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38. PLoS ONE 2015, 10, e0121510. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Y.; Yu, Z.; Wang, X.; Chen, W.; Liu, Y.; Zhang, Y.; Yin, J.; Han, S. Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum. Aging 2021. [Google Scholar] [CrossRef]
- Zeng, B.; Chen, T.; Xie, M.Y.; Luo, J.Y.; He, J.J.; Xi, Q.Y.; Sun, J.J.; Zhang, Y.L. Exploration of long noncoding RNA in bovine milk exosomes and their stability during digestion in vitro. J. Dairy Sci. 2019, 102, 6726–6737. [Google Scholar] [CrossRef]
- Zeng, B.; Chen, T.; Luo, J.; Xie, M.; Wei, L.; Xi, Q.; Sun, J.; Zhang, Y. Exploration of long non-coding RNAs and circular RNAs in porcine milk exosomes. Front. Genet. 2020, 11, 652. [Google Scholar] [CrossRef]
- Zhu, P.; Zhu, X.; Wu, J.; He, L.; Lu, T.; Wang, Y.; Liu, B.; Ye, B.; Sun, L.; Fan, D.; et al. IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat. Immunol. 2019, 20, 183–194. [Google Scholar] [CrossRef]
- Rankin, C.R.; Lokhandwala, Z.A.; Huang, R.; Pekow, J.; Pothoulakis, C.; Padua, D. Linear and circular CDKN2B-AS1 expression is associated with inflammatory bowel disease and participates in intestinal barrier formation. Life Sci. 2019, 231, 116571. [Google Scholar] [CrossRef]
- Marell, P.S.; Blohowiak, S.E.; Evans, M.D.; Georgieff, M.K.; Kling, P.J.; Tran, P.V. Cord blood-derived exosomal CNTN2 and BDNF: Potential molecular markers for brain health of neonates at risk for iron deficiency. Nutrients 2019, 11, 2478. [Google Scholar] [CrossRef] [Green Version]
- Lu, D.; Xu, A.D. Mini Review: Circular RNAs as potential clinical biomarkers for disorders in the central nervous system. Front. Genet. 2016, 7, 53. [Google Scholar] [CrossRef]
- Rich, B.S.; Dolgin, S.E. Necrotizing enterocolitis. Pediatr. Rev. 2017, 38, 552–559. [Google Scholar] [CrossRef]
- Jin, Y.T.; Duan, Y.; Deng, X.K.; Lin, J. Prevention of necrotizing enterocolitis in premature infants—An updated review. World J. Clin. Pediatr. 2019, 8, 23–32. [Google Scholar] [CrossRef]
- Markel, T.A.; Martin, C.A.; Chaaban, H.; Canvasser, J.; Tanner, H.; Denchik, H.; Good, M. New directions in necrotizing enterocolitis with early-stage investigators. Pediatr. Res. 2020, 88 (Suppl. S1), 35–40. [Google Scholar] [CrossRef]
- Chen, Y.; Koike, Y.; Chi, L.; Ahmed, A.; Miyake, H.; Li, B.; Lee, C.; Delgado-Olguín, P.; Pierro, A. Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis. Dis. Model. Mech. 2019, 12, dmm040998. [Google Scholar] [CrossRef] [Green Version]
- Neu, J.; Pammi, M. Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators. Semin. Fetal Neonatal Med. 2018, 23, 400–405. [Google Scholar] [CrossRef]
- Baranowski, J.R.; Claud, E.C. Necrotizing enterocolitis and the preterm infant microbiome. Adv. Exp. Med. Biol. 2019, 1125, 25–36. [Google Scholar] [PubMed]
- Martin, C.R.; Walker, W.A. Intestinal immune defences and the inflammatory response in necrotising enterocolitis. Semin. Fetal Neonatal Med. 2006, 11, 369–377. [Google Scholar] [CrossRef] [PubMed]
- Denning, T.L.; Bhatia, A.M.; Kane, A.F.; Patel, R.M.; Denning, P.W. Pathogenesis of NEC: Role of the innate and adaptive immune response. Semin. Perinatol. 2017, 41, 15–28. [Google Scholar] [CrossRef] [Green Version]
- Anand, R.J.; Leaphart, C.L.; Mollen, K.P.; Hackam, D.J. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock 2007, 27, 124–133. [Google Scholar] [CrossRef]
- Hackam, D.J.; Sodhi, C.P. Toll-like receptor-mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitis. Cell Mol. Gastroenterol. Hepatol. 2018, 6, 229–238. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Egan, C.E.; Sodhi, C.P.; Good, M.; Lin, J.; Jia, H.; Yamaguchi, Y.; Lu, P.; Ma, C.; Branca, M.F.; Weyandt, S.; et al. Toll-like receptor 4-mediated lymphocyte influxinduces neonatal necrotizing enterocolitis. J. Clin. Invest. 2016, 126, 495–508. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yazji, I.; Sodhi, C.P.; Lee, E.K.; Good, M.; Egan, C.E.; Afrazi, A.; Neal, M.D.; Jia, H.; Lin, J.; Ma, C.; et al. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS-NO-nitrite signaling. Proc. Natl. Acad. Sci. USA 2013, 110, 9451–9456. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, Y.; Koike, Y.; Miyake, H.; Li, B.; Lee, C.; Hock, A.; Zani, A.; Pierro, A. Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis. Pediatr. Surg. Int. 2016, 32, 1115–1119. [Google Scholar] [CrossRef]
- Ma, F.; Li, S.; Gao, X.; Zhou, J.; Zhu, X.; Wang, D.; Cai, Y.; Li, F.; Yang, Q.; Gu, X.; et al. Interleukin-6-mediated CCR9+interleukin-17-producing regulatory T cells polarization increases the severity of necrotizing enterocolitis. EBioMedicine 2019, 44, 71–85. [Google Scholar] [CrossRef] [Green Version]
- Pang, Y.; Du, X.; Xu, X.; Wang, M.; Li, Z. Monocyte activation and inflammation can exacerbate Treg/Th17 imbalance in infants with neonatal necrotizing enterocolitis. Int. Immunopharmacol. 2018, 59, 354–360. [Google Scholar] [CrossRef]
- Fituch, C.C.; Palkowetz, K.H.; Goldman, A.S.; Schanler, R.J. Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis. Acta Paediatr. 2004, 93, 1496–1500. [Google Scholar] [CrossRef]
- Chatterton, D.E.; Nguyen, D.N.; Bering, S.B.; Sangild, P.T. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int. J. Biochem. Cell Biol. 2013, 45, 1730–1747. [Google Scholar] [CrossRef]
- Shiou, S.R.; Yu, Y.; Guo, Y.; Westerhoff, M.; Lu, L.; Petrof, E.O.; Sun, J.; Claud, E.C. Oral administration of transforming growth factor-β1 (TGF-β1) protects the immature gut from injury via Smad protein-dependent suppression of epithelial nuclear factor κB (NF-κB) signaling and proinflammatory cytokine production. J. Biol. Chem. 2013, 288, 34757–34766. [Google Scholar] [CrossRef] [Green Version]
- Patel, A.L.; Kim, J.H. Human milk and necrotizing enterocolitis. Semin. Pediatr. Surg. 2018, 27, 34–38. [Google Scholar] [CrossRef]
- Ares, G.J.; McElroy, S.J.; Hunter, C.J. The science and necessity of using animal models in the study of necrotizing enterocolitis. Semin. Pediatr. Surg. 2018, 27, 29–33. [Google Scholar] [CrossRef]
- Siggers, R.H.; Siggers, J.; Thymann, T.; Boye, M.; Sangild, P.T. Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis. J. Nutr. Biochem. 2011, 22, 511–521. [Google Scholar] [CrossRef]
- Maffei, D.; Schanler, R.J. Human milk is the feeding strategy to prevent necrotizing enterocolitis! Semin. Perinatol. 2017, 41, 36–40. [Google Scholar] [CrossRef] [Green Version]
- Ou, J.; Courtney, C.M.; Steinberger, A.E.; Tecos, M.E.; Warner, B.W. Nutrition in necrotizing enterocolitis and following intestinal resection. Nutrients 2020, 12, 520. [Google Scholar] [CrossRef] [Green Version]
- Xu, A.T.; Lu, J.T.; Ran, Z.H.; Zheng, Q. Exosome in intestinal mucosal immunity. J. Gastroenterol. Hepatol. 2016, 31, 1694–1699. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Wang, X.; Yan, X.; Yu, Z.; Zhang, J.; Han, S. The emerging role of exosomes in the pathogenesis, prognosis and treatment of necrotizing enterocolitis. Am. J. Transl. Res. 2020, 12, 7020–7033. [Google Scholar]
- Martin, C.; Patel, M.; Williams, S.; Arora, H.; Brawner, K.; Sims, B. Human breast milk-derived exosomes attenuate cell death in intestinal epithelial cells. Innate Immun. 2018, 24, 278–284. [Google Scholar] [CrossRef] [PubMed]
- Pisano, C.; Galley, J.; Elbahrawy, M.; Wang, Y.; Farrell, A.; Brigstock, D.; Besner, G.E. Human breast milk-derived extracellular vesicles in the protection against experimental necrotizing enterocolitis. J. Pediatr. Surg. 2020, 55, 54–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Yan, X.; Zhang, L.; Cai, J.; Zhou, Y.; Liu, H.; Hu, Y.; Chen, W.; Xu, S.; Liu, P.; et al. Identification and peptidomic profiling of exosomes in preterm human milk: Insights into necrotizing enterocolitis prevention. Mol. Nutr. Food Res. 2019, 63, e1801247. [Google Scholar] [CrossRef] [PubMed]
- Wu, D.; Kittana, H.; Shu, J.; Kachman, S.D.; Cui, J.; Ramer-Tait, A.E.; Zempleni, J. Dietary depletion of milk exosomes and their microRNA cargos elicits a depletion of miR-200a-3p and elevated intestinal inflammation and chemokine (C-X-C motif) ligand 9 expression in Mdr1a-/- mice. Curr. Dev. Nutr. 2019, 3, nzz122. [Google Scholar]
- Stremmel, W.; Weiskirchen, R.; Melnik, B.C. Milk exosomes prevent intestinal inflammation in a genetic mouse model of ulcerative colitis: A pilot experiment. Inflamm. Intest. Dis. 2020, 5, 117–123. [Google Scholar] [CrossRef]
- Jiang, K.; Yang, J.; Yang, C.; Zhang, T.; Shaukat, A.; Yang, X.; Dai, A.; Wu, H.; Deng, G. miR-148a suppresses inflammation in lipopolysaccharide-induced endometritis. J. Cell. Mol. Med. 2020, 24, 405–417. [Google Scholar] [CrossRef] [Green Version]
- Zhu, Y.; Gu, L.; Li, Y.; Lin, X.; Shen, H.; Cui, K.; Chen, L.; Zhou, F.; Zhao, Q.; Zhang, J.; et al. miR-148a inhibits colitis and colitis-associated tumorigenesis in mice. Cell Death Differ. 2017, 24, 2199–2209. [Google Scholar] [CrossRef]
- Ashizawa, M.; Okayama, H.; Ishigame, T.; Thar Min, A.K.; Saito, K.; Ujiie, D.; Murakami, Y.; Kikuchi, T.; Nakayama, Y.; Noda, M.; et al. MiRNA-148a-3p regulates immunosuppression in DNA mismatch repair-deficient colorectal cancer by targeting PD-L1. Mol. Cancer Res. 2019, 17, 1403–1413. [Google Scholar]
- Murakami, M.; Narazaki, M.; Hibi, M.; Yawata, H.; Yasukawa, K.; Hamaguchi, M.; Taga, T.; Kishimoto, T. Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. Proc. Natl. Acad. Sci. USA 1991, 88, 11349–11353. [Google Scholar] [CrossRef] [Green Version]
- Taga, T.; Kishimoto, T. Gp130 and the interleukin-6 family of cytokines. Annu. Rev. Immunol. 1997, 15, 797–819. [Google Scholar] [CrossRef]
- Garbers, C.; Aparicio-Siegmund, S.; Rose-John, S. The IL-6/gp130/STAT3 signaling axis: Recent advances towards specific inhibition. Curr. Opin. Immunol. 2015, 34, 75–82. [Google Scholar] [CrossRef]
- Uciechowski, P.; Dempke, W.C.M. Interleukin-6: A masterplayer in the cytokine network. Oncology 2020, 98, 131–137. [Google Scholar] [CrossRef]
- Zschiedrich, I.; Hardeland, U.; Krones-Herzig, A.; Berriel Diaz, M.; Vegiopoulos, A.; Müggenburg, J.; Sombroek, D.; Hofmann, T.G.; Zawatzky, R.; Yu, X.; et al. Coactivator function of RIP140 for NFkappaB/RelA-dependent cytokine gene expression. Blood 2008, 112, 264–276. [Google Scholar] [CrossRef]
- Hu, F.; Wang, M.; Xiao, T.; Yin, B.; He, L.; Meng, W.; Dong, M.; Liu, F. miR-30 promotes thermogenesis and the development of beige fat by targeting RIP140. Diabetes 2015, 64, 2056–2068. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; John, S.M.; Carrera-Bastos, P.; Cordain, L. The impact of cow’s milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer. Nutr. Metab. 2012, 9, 74. [Google Scholar] [CrossRef] [Green Version]
- Song, Y.; Chavarro, J.E.; Cao, Y.; Qiu, W.; Mucci, L.; Sesso, H.D.; Stampfer, M.J.; Giovannucci, E.; Pollak, M.; Liu, S.; et al. Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians. J. Nutr. 2013, 143, 189–196. [Google Scholar] [CrossRef] [Green Version]
- Lu, W.; Chen, H.; Niu, Y.; Wu, H.; Xia, D.; Wu, Y. Dairy products intake and cancer mortality risk: A meta-analysis of 11 population-based cohort studies. Nutr. J. 2016, 15, 91. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; Schmitz, G. Exosomes of pasteurized milk: Potential pathogens of Western diseases. J. Transl. Med. 2019, 17, 3. [Google Scholar] [CrossRef] [Green Version]
- Aune, D.; Lau, R.; Chan, D.S.M.; Vieira, R.; Greenwood, D.C.; Kampman, E.; Norat, T. Dairy products and colorectal cancer risk: A systematic review and meta-analysis of cohort studies. Ann. Oncol. 2012, 23, 37–45. [Google Scholar] [CrossRef]
- Ralston, R.A.; Truby, H.; Palermo, C.E.; Walker, K.Z. Colorectal cancer and nonfermented milk, solid cheese, and fermented milk consumption: A systematic review and meta-analysis of prospective studies. Crit. Rev. Food Sci. Nutr. 2014, 54, 1167–1179. [Google Scholar] [CrossRef]
- Vieira, A.R.; Abar, L.; Chan, D.S.M.; Vingeliene, S.; Polemiti, E.; Stevens, C.; Greenwood, D.; Norat, T. Foods and beverages and colorectal cancer risk: A systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Ann. Oncol. 2017, 28, 1788–1802. [Google Scholar] [CrossRef] [PubMed]
- Dybos, S.A.; Flatberg, A.; Halgunset, J.; Viset, T.; Rolfseng, T.; Kvam, S.; Skogseth, H. Increased levels of serum miR-148a-3p are associated with prostate cancer. APMIS 2018, 126, 722–731. [Google Scholar] [CrossRef] [PubMed]
- Tsai, H.L.; Yang, I.P.; Huang, C.W.; Ma, C.J.; Kuo, C.H.; Lu, C.Y.; Juo, S.H.; Wang, J.Y. Clinical significance of microRNA-148a in patients with early relapse of stage II stage and III colorectal cancer after curative resection. Transl. Res. 2013, 162, 258–268. [Google Scholar] [CrossRef] [PubMed]
- Baltruskeviciene, E.; Schveigert, D.; Stankevicius, V.; Mickys, U.; Zvirblis, T.; Bublevic, J.; Suziedelis, K.; Aleknavicius, E. Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding. BMC Cancer 2017, 17, 607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eilebrecht, S.; Hotz-Wagenblatt, A.; Sarachaga, V.; Burk, A.; Falida, K.; Chakraborty, D.; Nikitina, E.; Tessmer, C.; Whitley, C.; Sauerland, C.; et al. Expression and replication of virus-like circular DNA in human cells. Sci. Rep. 2018, 8, 2851. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bund, T.; Nikitina, E.; Chakraborty, D.; Ernst, C.; Gunst, K.; Boneva, B.; Tessmer, C.; Volk, N.; Brobeil, A.; Weber, A.; et al. Analysis of chronic inflammatory lesions of the colon for BMMF Rep antigen expression and CD68 macrophage interactions. Proc. Natl. Acad. Sci. USA 2021, 118, e2025830118. [Google Scholar] [CrossRef] [PubMed]
- Gitto, E.; Marseglia, L.; Manti, S.; D’Angelo, G.; Barberi, I.; Salpietro, C.; Reiter, R.J. Protective role of melatonin in neonatal diseases. Oxid. Med. Cell. Longev. 2013, 2013, 980374. [Google Scholar] [CrossRef] [Green Version]
- D’Angelo, G.; Chimenz, R.; Reiter, R.J.; Gitto, E. Use of melatonin in oxidative stress related neonatal diseases. Antioxidants 2020, 9, 477. [Google Scholar] [CrossRef]
- Esteban-Zubero, E.; López-Pingarrón, L.; Alatorre-Jiménez, M.A.; Ochoa-Moneo, P.; Buisac-Ramón, C.; Rivas-Jiménez, M.; Castán-Ruiz, S.; Antoñanzas-Lombarte, Á.; Tan, D.X.; García, J.J.; et al. Melatonin’s role as a co-adjuvant treatment in colonic diseases: A review. Life Sci. 2017, 170, 72–81. [Google Scholar] [CrossRef] [Green Version]
- Kim, J.M.; Lee, S.Y.; Lee, J.Y. Melatonin for the prevention of fetal injury associated with intrauterine inflammation. Am. J. Reprod. Immunol. 2021, e13402. [Google Scholar] [CrossRef]
- Qin, Y.; Shi, W.; Zhuang, J.; Liu, Y.; Tang, L.; Bu, J.; Sun, J.; Bei, F. Variations in melatonin levels in preterm and term human breast milk during the first month after delivery. Sci. Rep. 2019, 9, 17984. [Google Scholar] [CrossRef]
- Guven, A.; Uysal, B.; Gundogdu, G.; Oztas, E.; Ozturk, H.; Korkmaz, A. Melatonin ameliorates necrotizing enterocolitis in a neonatal rat model. J. Pediatr. Surg. 2011, 46, 2101–2107. [Google Scholar] [CrossRef]
- Ma, F.; Hao, H.; Gao, X.; Cai, Y.; Zhou, J.; Liang, P.; Lv, J.; He, Q.; Shi, C.; Hu, D.; et al. Melatonin ameliorates necrotizing enterocolitis by preventing Th17/Treg imbalance through activation of the AMPK/SIRT1 pathway. Theranostics 2020, 10, 7730–7746. [Google Scholar] [CrossRef]
- Lacerda, J.Z.; Ferreira, L.C.; Lopes, B.C.; Aristizábal-Pachón, A.F.; Bajgelman, M.C.; Borin, T.F.; Zuccari, D.A.P.C. Therapeutic potential of melatonin in the regulation of miR-148a-3p and angiogenic factors in breast cancer. MicroRNA 2019, 8, 237–247. [Google Scholar] [CrossRef]
- Muroya, S.; Hagi, T.; Kimura, A.; Aso, H.; Matsuzaki, M.; Nomura, M. Lactogenic hormones alter cellular and extracellular microRNA expression in bovine mammary epithelial cell culture. J. Anim. Sci. Biotechnol. 2016, 7, 8. [Google Scholar] [CrossRef] [Green Version]
- Takeda, S.; Kuwabara, Y.; Mizuno, M. Concentrations and origin of oxytocin in breast milk. Endocrinol. Jpn. 1986, 33, 821–826. [Google Scholar] [CrossRef] [Green Version]
- Klein, B.Y.; Tamir, H.; Ludwig, R.J.; Glickstein, S.B.; Welch, M.G.; Anwar, M. Colostrum oxytocin modulates cellular stress response, inflammation, and autophagy markers in newborn rat gut villi. Biochem. Biophys. Res. Commun. 2017, 487, 47–53. [Google Scholar] [CrossRef]
- Gross Margolis, K.; Vittorio, J.; Talavera, M.; Gluck, K.; Li, Z.; Iuga, A.; Stevanovic, K.; Saurman, V.; Israelyan, N.; Welch, M.G.; et al. Enteric serotonin and oxytocin: Endogenous regulation of severity in a murine model of necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2017, 313, G386–G398. [Google Scholar] [CrossRef]
- Kosloske, A.M.; Ball, W.S., Jr.; Umland, E.; Skipper, B. Clostridial necrotizing enterocolitis. J. Pediatr. Surg. 1985, 20, 155–159. [Google Scholar] [CrossRef]
- Schönherr-Hellec, S.; Aires, J. Clostridia and necrotizing enterocolitis in preterm neonates. Anaerobe 2019, 58, 6–12. [Google Scholar] [CrossRef]
- Støy, A.C.; Mølbak, L.; Delègue, C.L.; Thymann, T.; Sangild, P.T.; Heegaard, P.M.; Manurung, S.; Skovgaard, K. Necrotizing enterocolitis in preterm pigs is associated with increased density of intestinal mucosa-associated bacteria including Clostridium perfringens. Neonatology 2015, 108, 188–195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, H.; Huang, X.; Yan, Z.; Yang, Q.; Wang, P.; Li, S.; Sun, W.; Gun, S. Effect of Clostridium perfringens type C on TLR4/MyD88/NF-κB signaling pathway in piglet small intestines. Microb. Pathog. 2019, 135, 103567. [Google Scholar] [CrossRef] [PubMed]
- Verstrepen, L.; Verhelst, K.; van Loo, G.; Carpentier, I.; Ley, S.C.; Beyaert, R. Expression, biological activities and mechanisms of action of A20 (TNFAIP3). Biochem. Pharmacol. 2010, 80, 2009–2020. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shembade, N.; Harhaj, E.W. Regulation of NF-κB signaling by the A20 deubiquitinase. Cell. Mol. Immunol. 2012, 9, 123–130. [Google Scholar] [CrossRef] [Green Version]
- Hammer, G.E.; Turer, E.E.; Taylor, K.E.; Fang, C.J.; Advincula, R.; Oshima, S.; Barrera, J.; Huang, E.J.; Hou, B.; Malynn, B.A.; et al. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat. Immunol. 2011, 12, 1184–1193. [Google Scholar] [CrossRef] [Green Version]
- Skotland, T.; Hessvik, N.P.; Sandvig, K.; Llorente, A. Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology. J. Lipid Res. 2019, 60, 9–18. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Chen, X.; Qian, Y.; Wang, X.; Zhou, Y.; Yan, X.; Yu, B.; Yao, S.; Yu, Z.; Zhu, J.; et al. Lipidomic profiling of human milk derived exosomes and their emerging Roles in the prevention of necrotizing enterocolitis. Mol. Nutr. Food Res. 2021, e2000845. [Google Scholar] [CrossRef]
- Yu, H.; Dilbaz, S.; Coßmann, J.; Hoang, A.C.; Diedrich, V.; Herwig, A.; Harauma, A.; Hoshi, Y.; Moriguchi, T.; Landgraf, K.; et al. Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages. J. Clin. Invest. 2019, 129, 2485–2499. [Google Scholar] [CrossRef] [Green Version]
- Phuyal, S.; Skotland, T.; Hessvik, N.P.; Simolin, H.; Øverbye, A.; Brech, A.; Parton, R.G.; Ekroos, K.; Sandvig, K.; Llorente, A. The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells. J. Biol. Chem. 2015, 290, 4225–4237. [Google Scholar] [CrossRef] [Green Version]
- Wallner, S.; Grandl, M.; Konovalova, T.; Sigrüner, A.; Kopf, T.; Peer, M.; Orsó, E.; Liebisch, G.; Schmitz, G. Monocyte to macrophage differentiation goes along with modulation of the plasmalogen pattern through transcriptional regulation. PLoS ONE 2014, 9, e94102. [Google Scholar] [CrossRef] [Green Version]
- Wallner, S.; Orsó, E.; Grandl, M.; Konovalova, T.; Liebisch, G.; Schmitz, G. Phosphatidylcholine and phosphatidylethanolamine plasmalogens in lipid loaded human macrophages. PLoS ONE 2018, 13, e0205706. [Google Scholar] [CrossRef]
- Zhao, H.; Shang, Q.; Pan, Z.; Bai, Y.; Li, Z.; Zhang, H.; Zhang, Q.; Guo, C.; Zhang, L.; Wang, Q. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes 2018, 67, 235–247. [Google Scholar] [CrossRef] [Green Version]
- Ikeda, K.; Maretich, P.; Kajimura, S. The common and distinct features of brown and beige adipocytes. Trends Endocrinol. Metab. 2018, 29, 191–200. [Google Scholar] [CrossRef] [Green Version]
- Rui, L. Brown and beige adipose tissues in health and disease. Compr. Physiol. 2017, 7, 1281–1306. [Google Scholar]
- Maghraby, M.K.; Li, B.; Chi, L.; Ling, C.; Benmoussa, A.; Provost, P.; Postmus, A.C.; Abdi, A.; Pierro, A.; Bourdon, C.; et al. Extracellular vesicles isolated from milk can improve gut barrier dysfunction induced by malnutrition. Sci. Rep. 2021, 11, 7635. [Google Scholar] [CrossRef]
- Auerbach, A.; Vyas, G.; Li, A.; Halushka, M.; Witwer, K. Uptake of dietary milk miRNAs by adult humans: A validation study. F1000Research 2016, 5, 721. [Google Scholar] [CrossRef]
- Lin, D.; Chen, T.; Xie, M.; Li, M.; Zeng, B.; Sun, R.; Zhu, Y.; Ye, D.; Wu, J.; Sun, J.; et al. Oral administration of bovine and porcine milk exosome alter miRNAs profiles in piglet serum. Sci. Rep. 2020, 10, 6983. [Google Scholar]
- Baier, S.R.; Nguyen, C.; Xie, F.; Wood, J.R.; Zempleni, J. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J. Nutr. 2014, 144, 1495–1500. [Google Scholar] [CrossRef]
- Wang, L.; Sadri, M.; Giraud, D.; Zempleni, J. RNase H2-dependent polymerase chain reaction and elimination of confounders in sample collection, storage, and analysis atrengthen evidence that microRNAs in bovine milk are bioavailable in humans. J. Nutr. 2018, 148, 153–159. [Google Scholar] [CrossRef] [Green Version]
- Aqil, F.; Munagala, R.; Jeyabalan, J.; Agrawal, A.K.; Kyakulaga, A.H.; Wilcher, S.A.; Gupta, R.C. Milk exosomes—Natural nanoparticles for siRNA delivery. Cancer Lett. 2019, 449, 186–195. [Google Scholar] [CrossRef]
- Agrawal, A.K.; Aqil, F.; Jeyabalan, J.; Spencer, W.A.; Beck, J.; Gachuki, B.W.; Alhakeem, S.S.; Oben, K.; Munagala, R.; Bondada, S.; et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 2017, 13, 1627–1636. [Google Scholar] [CrossRef] [PubMed]
- Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R.C. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 2016, 371, 48–61. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Betker, J.L.; Angle, B.M.; Graner, M.W.; Anchordoquy, T.J. The potential of exosomes from cow milk for oral delivery. J. Pharm. Sci. 2019, 108, 1496–1505. [Google Scholar] [CrossRef] [PubMed]
- Sedykh, S.; Kuleshova, A.; Nevinsky, G. Milk exosomes: Perspective agents for anticancer drug delivery. Int. J. Mol. Sci. 2020, 21, 6646. [Google Scholar] [CrossRef]
- Askenase, P.W. Ancient evolutionary origin and properties of universally produced natural exosomes contribute to their therapeutic superiority compared to artificial nanoparticles. Int. J. Mol. Sci. 2021, 22, 1429. [Google Scholar] [CrossRef]
- Del Pozo-Acebo, L.; Hazas, M.L.L.; Tomé-Carneiro, J.; Gil-Cabrerizo, P.; San-Cristobal, R.; Busto, R.; García-Ruiz, A.; Dávalos, A. Bovine milk-derived exosomes as a drug delivery vehicle for miRNA-based therapy. Int. J. Mol. Sci. 2021, 22, 1105. [Google Scholar] [CrossRef]
- Zempleni, J. Milk exosomes: Beyond dietary microRNAs. Genes Nutr. 2017, 12, 12. [Google Scholar] [CrossRef]
- Simeoni, U.; Yzydorczyk, C.; Siddeek, B.; Benahmed, M. Epigenetics and neonatal nutrition. Early Hum. Dev. 2014, 90 (Suppl. S2), S23–S24. [Google Scholar] [CrossRef]
- Reynolds, C.M.; Gray, C.; Li, M.; Segovia, S.A.; Vickers, M.H. Early life nutrition and energy balance disorders in offspring in later life. Nutrients 2015, 7, 8090–8111. [Google Scholar] [CrossRef]
- Canani, R.B.; Costanzo, M.D.; Leone, L.; Bedogni, G.; Brambilla, P.; Cianfarani, S.; Nobili, V.; Pietrobelli, A.; Agostoni, C. Epigenetic mechanisms elicited by nutrition in early life. Nutr. Res. Rev. 2011, 24, 198–205. [Google Scholar] [CrossRef]
- Marousez, L.; Lesage, J.; Eberlé, D. Epigenetics: Linking early postnatal nutrition to obesity programming? Nutrients 2019, 11, 2966. [Google Scholar] [CrossRef] [Green Version]
- Sosa-Castillo, E.; Rodríguez-Cruz, M.; Moltó-Puigmartí, C. Genomics of lactation: Role of nutrigenomics and nutrigenetics in the fatty acid composition of human milk. Br. J. Nutr. 2017, 118, 161–168. [Google Scholar] [CrossRef] [Green Version]
- Golan, Y.; Assaraf, Y.G. Genetic and physiological factors affecting human milk production and composition. Nutrients 2020, 12, 1500. [Google Scholar] [CrossRef]
- Hermann, A.; Goyal, R.; Jeltsch, A. The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J. Biol. Chem. 2004, 279, 48350–48359. [Google Scholar] [CrossRef] [Green Version]
- Li, E.; Zhang, Y. DNA methylation in mammals. Cold Spring Harb. Perspect. Biol. 2014, 6, a019133. [Google Scholar] [CrossRef]
- Güngör, D.; Nadaud, P.; LaPergola, C.C.; Dreibelbis, C.; Wong, Y.P.; Terry, N.; Abrams, S.A.; Beker, L.; Jacobovits, T.; Järvinen, K.M.; et al. Infant milk-feeding practices and food allergies, allergic rhinitis, atopic dermatitis, and asthma throughout the life span: A systematic review. Am. J. Clin. Nutr. 2019, 109 (Suppl. S7), 772S–799S. [Google Scholar] [CrossRef]
- Bion, V.; Lockett, G.A.; Soto-Ramírez, N.; Zhang, H.; Venter, C.; Karmaus, W.; Holloway, J.W.; Arshad, S.H. Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease. Allergy 2016, 71, 661–760. [Google Scholar] [CrossRef] [Green Version]
- Greer, F.R.; Sicherer, S.H.; Burks, A.W.; Committee on Nutrition; Section on Allergy and Immunology. The effects of early nutritional interventions on the development of atopic disease in infants and children: The role of maternal dietary restriction, breastfeeding, hydrolyzed formulas, and timing of introduction of allergenic complementary foods. Pediatrics 2019, 143, e20190281. [Google Scholar] [CrossRef] [Green Version]
- Sitarik, A.R.; Kasmikha, N.S.; Kim, H.; Wegienka, G.; Havstad, S.; Ownby, D.; Zoratti, E.; Johnson, C.C. Breast-feeding and delivery mode modify the association between maternal atopy and childhood allergic outcomes. J. Allergy Clin. Immunol. 2018, 142, 2002–2004. [Google Scholar] [CrossRef] [Green Version]
- Torregrosa Paredes, P.; Gutzeit, C.; Johansson, S.; Admyre, C.; Stenius, F.; Alm, J.; Scheynius, A.; Gabrielsson, S. Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle. Allergy 2014, 69, 463–471. [Google Scholar] [CrossRef]
- Simpson, M.R.; Brede, G.; Johansen, J.; Johnsen, R.; Storrø, O.; Sætrom, P.; Øien, T. Human breast milk miRNA, maternal probiotic supplementation and atopic dermatitis in offspring. PLoS ONE 2015, 10, e0143496. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shelke, G.V.; Yin, Y.; Jang, S.C.; Lässer, C.; Wennmalm, S.; Hoffmann, H.J.; Li, L.; Gho, Y.S.; Nilsson, J.A.; Lötvall, J. Endosomal signalling via exosome surface TGFβ-1. J. Extracell. Vesicles 2019, 8, 1650458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, W.; Jin, W.; Hardegen, N.; Lei, K.J.; Li, L.; Marinos, N.; McGrady, G.; Wahl, S.M. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med. 2003, 198, 1875–1886. [Google Scholar] [CrossRef] [PubMed]
- Takimoto, T.; Wakabayashi, Y.; Sekiya, T.; Inoue, N.; Morita, R.; Ichiyama, K.; Takahashi, R.; Asakawa, M.; Muto, G.; Mori, T.; et al. Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J. Immunol. 2010, 185, 842–855. [Google Scholar]
- Ito, M.; Iizuka-Koga, M.; Ando, M.; Yoshimura, A. Development and functional modulation of regulatory T cells by transcription factors and epigenetics. Cornea 2018, 37 (Suppl. S1), S42–S49. [Google Scholar] [CrossRef]
- Liao, H.; Peng, X.; Gan, L.; Feng, J.; Gao, Y.; Yang, S.; Hu, X.; Zhang, L.; Yin, Y.; Wang, H.; et al. Protective regulatory T cell immune response induced by intranasal immunization with the live-attenuated pneumococcal vaccine SPY1 via the transforming growth factor-β1-Smad2/3 pathway. Front. Immunol. 2018, 9, 1754. [Google Scholar] [CrossRef]
- Nazimek, K.; Bryniarski, K.; Askenase, P.W. Functions of exosomes and microbial extracellular vesicles in allergy and contact and delayed-type hypersensitivity. Int. Arch. Allergy Immunol. 2016, 171, 1–26. [Google Scholar] [CrossRef] [Green Version]
- Pegtel, D.M.; Gould, S.J. Exosomes. Annu. Rev. Biochem. 2019, 88, 487–514. [Google Scholar] [CrossRef]
- Le Doare, K.; Holder, B.; Bassett, A.; Pannaraj, P.S. Mother’s milk: A purposeful contribution to the development of the infant microbiota and immunity. Front. Immunol. 2018, 9, 361. [Google Scholar]
- Skogberg, G.; Telemo, E.; Ekwall, O. Exosomes in the thymus: Antigen transfer and vesicles. Front. Immunol. 2015, 6, 366. [Google Scholar] [CrossRef] [Green Version]
- Lundberg, V.; Berglund, M.; Skogberg, G.; Lindgren, S.; Lundqvist, C.; Gudmundsdottir, J.; Thörn, K.; Telemo, E.; Ekwall, O. Thymic exosomes promote the final maturation of thymocytes. Sci. Rep. 2016, 6, 36479. [Google Scholar] [CrossRef] [Green Version]
- Wang, G.J.; Liu, Y.; Qin, A.; Shah, S.V.; Deng, Z.B.; Xiang, X.; Cheng, Z.; Liu, C.; Wang, J.; Zhang, L.; et al. Thymus exosomes-like particles induce regulatory T cells. J. Immunol. 2008, 181, 5242–5248. [Google Scholar] [CrossRef] [Green Version]
- Peroni, D.G.; Piacentini, G.L.; Bodini, A.; Pigozzi, R.; Boner, A.L. Transforming growth factor-beta is elevated in unpasteurized cow’s milk. Pediatr. Allergy Immunol. 2009, 20, 42–44. [Google Scholar]
- Jones, J.G. Hepatic glucose and lipid metabolism. Diabetologia 2016, 59, 1098–1103. [Google Scholar] [CrossRef] [Green Version]
- Kubes, P.; Jenne, C. Immune responses in the liver. Annu. Rev. Immunol. 2018, 36, 247–277. [Google Scholar] [CrossRef]
- Pyzik, M.; Rath, T.; Kuo, T.T.; Win, S.; Baker, K.; Hubbard, J.J.; Grenha, R.; Gandhi, A.; Krämer, T.D.; Mezo, A.R.; et al. Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proc. Natl. Acad. Sci. USA 2017, 114, E2862–E2871. [Google Scholar] [CrossRef] [Green Version]
- Latvala, S.; Jacobsen, B.; Otteneder, M.B.; Herrmann, A.; Kronenberg, S. Distribution of FcRn across species and tissues. J. Histochem. Cytochem. 2017, 65, 321–333. [Google Scholar] [CrossRef] [Green Version]
- Fan, Y.Y.; Farrokhi, V.; Caiazzo, T.; Wang, M.; O’Hara, D.M.; Neubert, H. Human FcRn tissue expression profile and half-life in PBMCs. Biomolecules 2019, 9, 373. [Google Scholar] [CrossRef] [Green Version]
- Devhare, P.B.; Sasaki, R.; Shrivastava, S.; Di Bisceglie, A.M.; Ray, R.; Ray, R.B. Exosome-mediated intercellular communication between hepatitis C virus-infected hepatocytes and hepatic stellate cells. J. Virol. 2017, 91, e02225–e02316. [Google Scholar] [CrossRef] [Green Version]
- Weiskirchen, R.; Tacke, F. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology. Hepatobiliary Surg. Nutr. 2014, 3, 344–363. [Google Scholar]
- Li, L.; Hu, W.; Liu, K.; Zhang, D.; Liu, M.; Li, X.; Wang, H. miR-148a/LDLR mediates hypercholesterolemia induced by prenatal dexamethasone exposure in male offspring rats. Toxicol. Appl. Pharmacol. 2020, 395, 114979. [Google Scholar] [CrossRef]
- Mersey, B.D.; Jin, P.; Danner, D.J. Human microRNA (miR29b) expression controls the amount of branched chain alpha-ketoacid dehydrogenase complex in a cell. Hum. Mol. Genet. 2005, 14, 3371–3377. [Google Scholar] [CrossRef]
- Kimball, S.R.; Jefferson, L.S. Regulation of protein synthesis by branched-chain amino acids. Curr. Opin. Clin. Nutr. Metab. Care 2001, 4, 39–43. [Google Scholar] [CrossRef]
- Suryawan, A.; Davis, T.A. Regulation of protein synthesis by amino acids in muscle of neonates. Front. Biosci. 2011, 16, 1445–1460. [Google Scholar] [CrossRef] [Green Version]
- Ijichi, C.; Matsumura, T.; Tsuji, T.; Eto, Y. Branched-chain amino acids promote albumin synthesis in rat primary hepatocytes through the mTOR signal transduction system. Biochem. Biophys. Res. Commun. 2003, 303, 59–64. [Google Scholar] [CrossRef]
- Horta, B.L.; Loret de Mola, C.; Victora, C.G. Breastfeeding and intelligence: A systematic review and meta-analysis. Acta Paediatr. 2015, 104, 14–19. [Google Scholar] [CrossRef]
- Koh, K. Maternal breastfeeding and children’s cognitive development. Soc. Sci. Med. 2017, 187, 101–108. [Google Scholar] [CrossRef]
- Keim, S.A.; Sullivan, J.A.; Sheppard, K.; Smith, K.; Ingol, T.; Boone, K.M.; Malloy-McCoy, A.; Oza-Frank, R. Feeding infants at the breast or feeding expressed human milk: Long-term cognitive, executive function, and eating behavior outcomes at age 6 years. J. Pediatr. 2021. [Google Scholar] [CrossRef]
- Kramer, M.S.; Aboud, F.; Mironova, E.; Vanilovich, I.; Platt, R.W.; Matush, L.; Igumnov, S.; Fombonne, E.; Bogdanovich, N.; Ducruet, T.; et al. Promotion of Breastfeeding Intervention Trial (PROBIT) Study Group. Breastfeeding and child cognitive development: New evidence from a large randomized trial. Arch. Gen. Psychiatry 2008, 65, 578–584. [Google Scholar]
- Horta, B.L.; de Sousa, B.A.; de Mola, C.L. Breastfeeding and neurodevelopmental outcomes. Curr. Opin. Clin. Nutr. Metab. Care 2018, 21, 174–178. [Google Scholar] [CrossRef]
- Chen, C.C.; Liu, L.; Ma, F.; Wong, C.W.; Guo, X.E.; Chacko, J.V.; Farhoodi, H.P.; Zhang, S.X.; Zimak, J.; Ségaliny, A.; et al. Elucidation of exosome migration across the blood-brain barrier model in vitro. Cell. Mol. Bioeng. 2016, 9, 509–529. [Google Scholar] [CrossRef] [PubMed]
- Patel, M.M.; Patel, B.M. Crossing the blood-brain barrier: Recent advances in drug delivery to the brain. CNS Drugs 2017, 31, 109–133. [Google Scholar] [CrossRef] [PubMed]
- Jakubec, M.; Maple-Grødem, J.; Akbari, S.; Nesse, S.; Halskau, Ø.; Mork-Jansson, A.E. Plasma-derived exosome-like vesicles are enriched in lyso-phospholipids and pass the blood-brain barrier. PLoS ONE 2020, 15, e0232442. [Google Scholar] [CrossRef] [PubMed]
- Saint-Pol, J.; Gosselet, F.; Duban-Deweer, S.; Pottiez, G.; Karamanos, Y. Targeting and crossing the blood-brain barrier with extracellular vesicles. Cells 2020, 9, 851. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bouret, S.G. Nutritional programming of hypothalamic development: Critical periods and windows of opportunity. Int. J. Obes. Suppl. 2012, 2 (Suppl. S2), S19–S24. [Google Scholar] [CrossRef]
- Jakowec, M.W.; Donaldson, D.M.; Barba, J.; Petzinger, G.M. Postnatal expression of alpha-synuclein protein in the rodent substantia nigra and striatum. Dev. Neurosci. 2001, 23, 91–99. [Google Scholar] [CrossRef]
- Yavich, L.; Tanila, H.; Vepsäläinen, S.; Jäkälä, P. Role of alpha-synuclein in presynaptic dopamine recruitment. J. Neurosci. 2004, 24, 11165–11170. [Google Scholar] [CrossRef] [Green Version]
- Burré, J. The synaptic function of α-synuclein. J. Parkinsons Dis. 2015, 5, 699–713. [Google Scholar] [CrossRef] [Green Version]
- Burré, J.; Sharma, M.; Südhof, T.C. Cell biology and pathophysiology of α-synuclein. Cold Spring Harb. Perspect. Med. 2018, 8, a024091. [Google Scholar] [CrossRef]
- Sulzer, D.; Edwards, R.H. The physiological role of α-synuclein and its relationship to Parkinson’s Disease. J. Neurochem. 2019, 150, 475–486. [Google Scholar] [CrossRef] [Green Version]
- Westphal, C.H.; Chandra, S.S. Monomeric synucleins generate membrane curvature. J. Biol. Chem. 2013, 288, 1829–1840. [Google Scholar] [CrossRef] [Green Version]
- Burré, J.; Sharma, M.; Tsetsenis, T.; Buchman, V.; Etherton, M.R.; Südhof, T.C. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010, 329, 1637–1663. [Google Scholar] [CrossRef] [Green Version]
- Lou, X.; Kim, J.; Hawk, B.J.; Shin, Y.K. α-Synuclein may cross-bridge v-SNARE and acidic phospholipids to facilitate SNAREdependent vesicle docking. Biochem. J. 2017, 474, 2039–2049. [Google Scholar] [CrossRef] [Green Version]
- Xiong, Q.Y.; Yu, C.; Zhang, Y.; Ling, L.; Wang, L.; Gao, J.L. Key proteins involved in insulin vesicle exocytosis and secretion. Biomed. Rep. 2017, 6, 134–139. [Google Scholar] [CrossRef] [Green Version]
- Varkey, J.; Isas, J.M.; Mizuno, N.; Jensen, M.B.; Bhatia, V.K.; Jao, C.C.; Petrlova, J.; Voss, J.C.; Stamou, D.G.; Steven, A.C.; et al. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins. J. Biol. Chem. 2010, 285, 32486–32493. [Google Scholar] [CrossRef] [Green Version]
- Mor, D.E.; Tsika, E.; Mazzulli, J.R.; Gould, N.S.; Kim, H.; Daniels, M.J.; Doshi, S.; Gupta, P.; Grossman, J.L.; Tan, V.X.; et al. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration. Nat. Neurosci. 2017, 20, 1560–1568. [Google Scholar] [CrossRef]
- Zhang, J.; Li, X.; Li, J.D. The roles of post-translational modifications on α-synuclein in the pathogenesis of Parkinson’s diseases. Front. Neurosci. 2019, 13, 381. [Google Scholar] [CrossRef] [Green Version]
- Xu, J.; Camfield, R.; Gorski, S.M. The interplay between exosomes and autophagy-Partners in crime. J. Cell Sci. 2018, 131, jcs215210. [Google Scholar] [CrossRef] [Green Version]
- Matsumoto, L.; Takuma, H.; Tamaoka, A.; Kurisaki, H.; Date, H.; Tsuji, S.; Iwata, A. CpG demethylation enhances alphasynuclein expression and affects the pathogenesis of Parkinson’s disease. PLoS ONE 2010, 5, e15522. [Google Scholar] [CrossRef] [Green Version]
- Desplats, P.; Spencer, B.; Coffee, E.; Patel, P.; Michael, S.; Patrick, C.; Adame, A.; Rockenstein, E.; Masliah, E. Alpha-synuclein sequesters Dnmt1 from the nucleus: A novel mechanism for epigenetic alterations in Lewy body diseases. J. Biol. Chem. 2011, 286, 9031–9037. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Wang, X.; Li, R.; Yang, Z.F.; Wang, Y.Z.; Gong, X.L.; Wang, X.M. A DNA methyltransferase inhibitor, 5-aza-2’-deoxycytidine, exacerbates neurotoxicity and upregulates Parkinson’s disease-related genes in dopaminergic neurons. CNS Neurosci. Ther. 2013, 19, 183–190. [Google Scholar] [CrossRef] [PubMed]
- Jiang, W.; Li, J.; Zhang, Z.; Wang, H.; Wang, Z. Epigenetic upregulation of alpha-synuclein in the rats exposed to methamphetamine. Eur. J. Pharmacol. 2014, 745, 243–248. [Google Scholar] [CrossRef] [PubMed]
- Tan, Y.Y.; Wu, L.; Zhao, Z.B.; Wang, Y.; Xiao, Q.; Liu, J.; Wang, G.; Ma, J.F.; Chen, S.D. Methylation of α-synuclein and leucine-rich repeat kinase 2 in leukocyte DNA of Parkinson’s disease patients. Parkinsonism Relat. Disord. 2014, 20, 308–313. [Google Scholar] [CrossRef]
- Muller, T.; Kohlhepp, W. Hypomethylation in Parkinson’s disease: An epigenetic drug effect? Mov. Disord. 2016, 31, 605. [Google Scholar] [CrossRef] [PubMed]
- Wullner, U.; Kaut, O.; deBoni, L.; Piston, D.; Schmitt, I. DNA methylation in Parkinson’s disease. J. Neurochem. 2016, 139 (Suppl. S1), 108–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guhathakurta, S.; Bok, E.; Evangelista, B.A.; Kim, Y.S. Deregulation of α-synuclein in Parkinson’s disease: Insight from epigenetic structure and transcriptional regulation of SNCA. Prog. Neurobiol. 2017, 154, 21–36. [Google Scholar] [CrossRef] [PubMed]
- Eryilmaz, I.E.; Cecener, G.; Erer, S.; Egeli, U.; Tunca, B.; Zarifoglu, M.; Elibol, B.; Bora Tokcaer, A.; Saka, E.; Demirkiran, M.; et al. Epigenetic approach to early-onset Parkinson’s disease: Low methylation status of SNCA and PARK2 promoter regions. Neurol. Res. 2017, 39, 965–972. [Google Scholar] [CrossRef] [PubMed]
- Melnik, B.C. Synergistic effects of milk-derived exosomes and galactose on α-synuclein pathology in Parkinson’s disease and type 2 diabetes mellitus. Int. J. Mol. Sci. 2021, 22, 1059. [Google Scholar] [CrossRef]
- Mutai, E.; Zhou, F.; Zempleni, J. Depletion of dietary bovine milk exosomes impairs sensorimotor gating and spatial learning in C57BL/6 mice. FASEB J. 2018, 31, S1. [Google Scholar]
- Martínez, J.A.; Cordero, P.; Campión, J.; Milagro, F.I. Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes. Proc. Nutr. Soc. 2012, 71, 276–283. [Google Scholar] [CrossRef] [Green Version]
- Jermendy, A.; Toschi, E.; Aye, T.; Koh, A.; Aguayo-Mazzucato, C.; Sharma, A.; Weir, G.C.; Sgroi, D.; Bonner-Weir, S. Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells. Diabetologia 2011, 54, 594–604. [Google Scholar] [CrossRef] [Green Version]
- Finegood, D.T.; Scaglia, L.; Bonner-Weir, S. Dynamics of beta-cell mass in the growing rat pancreas. Estimation with a simple mathematical model. Diabetes 1995, 44, 249–256. [Google Scholar] [CrossRef]
- Gregg, B.E.; Moore, P.C.; Demozay, D.; Hall, B.A.; Li, M.; Husain, A.; Wright, A.J.; Atkinson, M.A.; Rhodes, C.J. Formation of a human β-cell population within pancreatic islets is set early in life. J. Clin. Endocrinol. Metab. 2012, 97, 3197–3206. [Google Scholar] [CrossRef]
- Zeng, C.; Mulas, F.; Sui, Y.; Guan, T.; Miller, N.; Tan, Y.; Liu, F.; Jin, W.; Carrano, A.C.; Huising, M.O.; et al. Pseudotemporal ordering of single cells reveals metabolic control of postnatal β cell proliferation. Cell Metab. 2017, 25, 1160–1175. [Google Scholar] [CrossRef] [Green Version]
- Deng, Z.B.; Poliakov, A.; Hardy, R.W.; Clements, R.; Liu, C.; Liu, Y.; Wang, J.; Xiang, X.; Zhang, S.; Zhuang, X.; et al. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 2009, 58, 2498–2505. [Google Scholar] [CrossRef] [Green Version]
- Jalabert, A.; Vial, G.; Guay, C.; Wiklander, O.P.; Nordin, J.Z.; Aswad, H.; Forterre, A.; Meugnier, E.; Pesenti, S.; Regazzi, R.; et al. Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice. Diabetologia 2016, 59, 1049–1058. [Google Scholar] [CrossRef] [Green Version]
- Guay, C.; Regazzi, R. Exosomes as new players in metabolic organ cross-talk. Diabetes Obes. Metab. 2017, 19 (Suppl. S1), 137–146. [Google Scholar] [CrossRef]
- Sun, Y.; Shi, H.; Yin, S.; Ji, C.; Zhang, X.; Zhang, B.; Wu, P.; Shi, Y.; Mao, F.; Yan, Y.; et al. Human mesenchymal stem cell derived exosomes alleviate type 2 diabetes mellitus by reversing peripheral insulin resistance and relieving β-cell destruction. ACS Nano 2018, 12, 7613–7628. [Google Scholar] [CrossRef]
- Ge, Q.; Xie, X.X.; Xiao, X.; Li, X. Exosome-like vesicles as new mediators and therapeutic targets for treating insulin resistance and β-cell mass failure in type 2 diabetes mellitus. J. Diabetes Res. 2019, 2019, 3256060. [Google Scholar] [CrossRef] [Green Version]
- Marzan, A.L.; Nedeva, C.; Mathivanan, S. Extracellular vesicles in metabolism and metabolic diseases. Subcell. Biochem. 2021, 97, 393–410. [Google Scholar]
- Melnik, B.C. The pathogenic role of persistent milk signaling in mTORC1- and milk- microRNA-driven type 2 diabetes mellitus. Curr. Diabetes Rev. 2015, 11, 46–62. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Melnik, B.C. Milk exosomal miRNAs: Potential drivers of AMPK-to-mTORC1 switching in β-cell de-differentiation of type 2 diabetes mellitus. Nutr. Metab. 2019, 16, 85. [Google Scholar] [CrossRef] [PubMed]
- Ardestani, A.; Lupse, B.; Kido, Y.; Leibowitz, G.; Maedler, K. mTORC1 signaling: A double-edged sword in diabetic β cells. Cell. Metab. 2018, 27, 314–331. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, F.; Wei, Z.; Shi, C.; Gan, Y.; Lu, J.; Frank, S.J.; Balducci, J.; Huang, Y. Signaling cross talk between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in pancreatic islet β-cells. Mol. Endocrinol. 2011, 25, 2119–2133. [Google Scholar] [CrossRef] [Green Version]
- Huang, Y.; Chang, Y. Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling. Prog. Mol. Biol. Transl. Sci. 2014, 121, 321–349. [Google Scholar]
- Wang, Y.; Sun, J.; Ni, Q.; Nie, A.; Gu, Y.; Wang, S.; Zhang, W.; Ning, G.; Wang, W.; Wang, Q. Dual effect of raptor on neonatal β-cell proliferation and identity maintenance. Diabetes 2019, 68, 1950–1964. [Google Scholar] [CrossRef]
- Jaafar, R.; Tran, S.; Shah, A.N.; Sun, G.; Valdearcos, M.; Marchetti, P.; Masini, M.; Swisa, A.; Giacometti, S.; Bernal-Mizrachi, E.; et al. mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes. J. Clin. Invest. 2019, 129, 4124–4137. [Google Scholar] [CrossRef] [Green Version]
- Gao, W.; Ge, S.; Sun, J. Ailanthone exerts anticancer effect by up-regulating miR-148a expression in MDA-MB-231 breast cancer cells and inhibiting proliferation, migration and invasion. Biomed. Pharmacother. 2019, 109, 1062–1069. [Google Scholar] [CrossRef]
- Chakravarthy, H.; Gu, X.; Enge, M.; Dai, X.; Wang, Y.; Damond, N.; Downie, C.; Liu, K.; Wang, J.; Xing, Y.; et al. Converting adult pancreatic islet α cells into β cells by targeting both Dnmt1 and Arx. Cell. Metab. 2017, 25, 622–634. [Google Scholar] [CrossRef] [Green Version]
- De Candia, P.; Spinetti, G.; Specchia, C.; Sangalli, E.; La Sala, L.; Uccellatore, A.; Lupini, S.; Genovese, S.; Matarese, G.; Ceriello, A. A unique plasma microRNA profile defines type 2 diabetes progression. PLoS ONE 2017, 12, e0188980. [Google Scholar] [CrossRef] [Green Version]
- Mirza, A.H.; Kaur, S.; Nielsen, L.B.; Størling, J.; Yarani, R.; Roursgaard, M.; Mathiesen, E.R.; Damm, P.; Svare, J.; Mortensen, H.B.; et al. Breast milk-derived extracellular vesicles enriched in exosomes from mothers with type 1 diabetes contain aberrant levels of microRNAs. Front. Immunol. 2019, 10, 2543. [Google Scholar] [CrossRef]
- Xue, L.J.; Huang, Q.; Zeng, J.E.; Zhu, H.; Xu, C.Y. Up-regulation of receptor interaction protein 140 promotes glucolipotoxicity-induced damage in MIN6 cells. Cell. Mol. Biol. 2018, 64, 39–45. [Google Scholar] [CrossRef]
- Yan, J.; Liu, L.; Zhu, Y.; Huang, G.; Wang, P.P. The association between breastfeeding and childhood obesity: A meta-analysis. BMC Public Health 2014, 14, 1267. [Google Scholar] [CrossRef] [Green Version]
- Iguacel, I.; Monje, L.; Cabero, M.J.; Moreno Aznar, L.A.; Samper, M.P.; Rodríguez-Palmero, M.; Rivero, M.; Rodríguez, G. Feeding patterns and growth trajectories in breast-fed and formula-fed infants during the introduction of complementary food. Nutr. Hosp. 2019, 36, 777–785. [Google Scholar] [CrossRef]
- Rito, A.I.; Buoncristiano, M.; Spinelli, A.; Salanave, B.; Kunešová, M.; Hejgaard, T.; García Solano, M.; Fijałkowska, A.; Sturua, L.; Hyska, J.; et al. Association between characteristics at birth, breastfeeding and obesity in 22 countries: The WHO European Childhood Obesity Surveillance Initiative—COSI 2015/2017. Obes. Facts 2019, 12, 226–243. [Google Scholar] [CrossRef] [Green Version]
- Qiao, J.; Dai, L.J.; Zhang, Q.; Ouyang, Y.Q. A meta-analysis of the association between breastfeeding and early childhood obesity. J. Pediatr. Nurs. 2020, 53, 57–66. [Google Scholar] [CrossRef]
- Pope, M.; Budge, H.; Symonds, M.E. The developmental transition of ovine adipose tissue through early life. Acta Physiol. 2014, 210, 20–30. [Google Scholar] [CrossRef]
- Villatoro, A.J.; Martín-Astorga, M.D.C.; Alcoholado, C.; Becerra, J. Canine colostrum exosomes: Characterization and influence on the canine mesenchymal stem cell secretory profile and fibroblast anti-oxidative capacity. BMC Vet. Res. 2020, 16, 417. [Google Scholar] [CrossRef]
- Shah, K.B.; Chernausek, S.D.; Garman, L.D.; Pezant, N.P.; Plows, J.F.; Kharoud, H.K.; Demerath, E.W.; Fields, D.A. Human Milk Exosomal MicroRNA: Associations with maternal overweight/obesity and infant body composition at 1 month of life. Nutrients 2021, 13, 1091. [Google Scholar] [CrossRef]
- Shabalina, I.G.; Petrovic, N.; de Jong, J.M.; Kalinovich, A.V.; Cannon, B.; Nedergaard, J. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell. Rep. 2013, 5, 1196–1203. [Google Scholar] [CrossRef] [Green Version]
- Bartesaghi, S.; Hallen, S.; Huang, L.; Svensson, P.A.; Momo, R.A.; Wallin, S.; Carlsson, E.K.; Forslöw, A.; Seale, P.; Peng, X.R. Thermogenic activity of UCP1 in human white fat-derived beige adipocytes. Mol. Endocrinol. 2015, 29, 130–139. [Google Scholar] [CrossRef] [Green Version]
- Shore, A.; Karamitri, A.; Kemp, P.; Speakman, J.R.; Lomax, M.A. Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue. Diabetologia 2010, 53, 1164–1173. [Google Scholar] [CrossRef] [Green Version]
- Hayashi, K.; Funaba, M.; Murakami, M. Tissue-dependent DNA methylation of carp uncoupling protein 1 promoter. Physiol. Genomics 2019, 51, 623–629. [Google Scholar] [CrossRef]
- Kiskinis, E.; Hallberg, M.; Christian, M.; Olofsson, M.; Dilworth, S.M.; White, R.; Parker, M.G. RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes. EMBO J. 2007, 26, 4831–4840. [Google Scholar] [CrossRef]
- Xi, Y.; Jiang, X.; Li, R.; Chen, M.; Song, W.; Li, X. The levels of human milk microRNAs and their association with maternal weight characteristics. Eur. J. Clin. Nutr. 2016, 70, 445–449. [Google Scholar] [CrossRef]
- Hallberg, M.; Morganstein, D.L.; Kiskinis, E.; Shah, K.; Kralli, A.; Dilworth, S.M.; White, R.; Parker, M.G.; Christian, M. A functional interaction between RIP140 and PGC-1alpha regulates the expression of the lipid droplet protein CIDEA. Mol. Cell. Biol. 2008, 28, 6785–6795. [Google Scholar] [CrossRef] [Green Version]
- Scarpulla, R.C.; Vega, R.B.; Kelly, D.P. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol. Metab. 2012, 23, 459–466. [Google Scholar] [CrossRef] [Green Version]
- Villena, J.A. New insights into PGC-1 coactivators: Redefining their role in the regulation of mitochondrial function and beyond. FEBS J. 2015, 282, 647–672. [Google Scholar] [CrossRef]
- Leonardsson, G.; Steel, J.H.; Christian, M.; Pocock, V.; Milligan, S.; Bell, J.; So, P.W.; Medina-Gomez, G.; Vidal-Puig, A.; White, R.; et al. Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc. Natl. Acad. Sci. USA 2004, 101, 8437–8442. [Google Scholar] [CrossRef] [Green Version]
- White, R.; Morganstein, D.; Christian, M.; Seth, A.; Herzog, B.; Parker, M.G. Role of RIP140 in metabolic tissues: Connections to disease. FEBS Lett. 2008, 582, 39–45. [Google Scholar] [CrossRef] [Green Version]
- Fritah, A.; Christian, M.; Parker, M.G. The metabolic coregulator RIP140: An update. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E335–E340. [Google Scholar] [CrossRef] [PubMed]
- Mota de Sá, P.; Richard, A.J.; Hang, H.; Stephens, J.M. Transcriptional regulation of adipogenesis. Compr. Physiol. 2017, 7, 635–674. [Google Scholar] [PubMed]
- Chen, Y.; Siegel, F.; Kipschull, S.; Haas, B.; Fröhlich, H.; Meister, G.; Pfeifer, A. miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit. Nat. Commun. 2013, 4, 1769. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gharanei, S.; Shabir, K.; Brown, J.E.; Weickert, M.O.; Barber, T.M.; Kyrou, I.; Randeva, H.S. Regulatory microRNAs in brown, brite and white adipose tissue. Cells 2020, 9, 2489. [Google Scholar] [CrossRef]
- Shi, C.; Zhang, M.; Tong, M.; Yang, L.; Pang, L.; Chen, L.; Xu, G.; Chi, X.; Hong, Q.; Ni, Y.; et al. miR-148a is associated with obesity and modulates adipocyte differentiation of mesenchymal stem cells through Wnt signaling. Sci. Rep. 2015, 5, 9930. [Google Scholar] [CrossRef] [Green Version]
- Shi, C.; Huang, F.; Gu, X.; Zhang, M.; Wen, J.; Wang, X.; You, L.; Cui, X.; Ji, C.; Guo, X. Adipogenic miRNA and meta-signature miRNAs involved in human adipocyte differentiation and obesity. Oncotarget 2016, 7, 40830–40845. [Google Scholar] [CrossRef] [Green Version]
- Cho, Y.M.; Kim, T.M.; Hun Kim, D.; Hee Kim, D.; Jeong, S.W.; Kwon, O.J. miR-148a is a downstream effector of X-box-binding protein 1 that silences Wnt10b during adipogenesis of 3T3-L1 cells. Exp. Mol. Med. 2016, 48, e226. [Google Scholar] [CrossRef]
- Tian, L.; Zheng, F.; Li, Z.; Wang, H.; Yuan, H.; Zhang, X.; Ma, Z.; Li, X.; Gao, X.; Wang, B. miR-148a-3p regulates adipocyte and osteoblast differentiation by targeting lysine-specific demethylase 6b. Gene 2017, 627, 32–39. [Google Scholar] [CrossRef]
- He, H.; Cai, M.; Zhu, J.; Xiao, W.; Liu, B.; Shi, Y.; Yang, X.; Liang, X.; Zheng, T.; Hu, S.; et al. miR-148a-3p promotes rabbit preadipocyte differentiation by targeting PTEN. In Vitro Cell. Dev. Biol. Anim. 2018, 54, 241–249. [Google Scholar] [CrossRef]
- Jin, X.; Hao, Z.; Zhao, M.; Shen, J.; Ke, N.; Song, Y.; Qiao, L.; Lu, Y.; Hu, L.; Wu, X.; et al. MicroRNA-148a regulates the proliferation and differentiation of ovine preadipocytes by targeting PTEN. Animals 2021, 11, 820. [Google Scholar] [CrossRef]
- Yi, T.; Choi, H.M.; Park, R.W.; Sohn, K.Y.; Kim, I.S. Transcriptional repression of type I procollagen genes during adipocyte differentiation. Exp. Mol. Med. 2001, 33, 269–275. [Google Scholar] [CrossRef]
- Liu, X.; Long, X.; Gao, Y.; Liu, W.; Hayashi, T.; Mizuno, K.; Hattori, S.; Fujisaki, H.; Ogura, T.; Onodera, S.; et al. Type I collagen inhibits adipogenic differentiation via YAP activation in vitro. J. Cell. Physiol. 2020, 235, 1821–1837. [Google Scholar] [CrossRef]
- Xiong, J.; Ni, J.; Chen, C.; Wang, K. miR 148a 3p regulates alcoholic liver fibrosis through targeting ERBB3. Int. J. Mol. Med. 2020, 46, 1003–1012. [Google Scholar] [CrossRef]
- Song, W.; Zhong, C.; Yuan, Y.; Zhu, Q.; Wang, Y.; Yin, H.; Li, D.; Zhang, Z.; Shu, G.; Yang, C.; et al. Peroxisome proliferator-activated receptor-coactivator 1-beta (PGC-1β) modulates the expression of genes involved in adipogenesis during preadipocyte differentiation in chicken. Gene 2020, 741, 144516. [Google Scholar] [CrossRef]
- Kamei, Y.; Ohizumi, H.; Fujitani, Y.; Nemoto, T.; Tanaka, T.; Takahashi, N.; Kawada, T.; Miyoshi, M.; Ezaki, O.; Kakizuka, A. PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc. Natl. Acad. Sci. USA 2003, 100, 12378–12383. [Google Scholar] [CrossRef] [Green Version]
- Ji, H.; Lu, R.H.; Chang, Z.G.; Su, S.S.; Yang, G.S. PGC-1β modulates the expression of genes involved in mitochondrial function and adipogenesis during preadipocyte differentiation. Reprod. Domest. Anim. 2012, 47, 419–427. [Google Scholar] [CrossRef]
- Scarpulla, R.C. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim. Biophys. Acta 2011, 1813, 1269–1278. [Google Scholar] [CrossRef] [Green Version]
- Fuller-Jackson, J.P.; Henry, B.A. Adipose and skeletal muscle thermogenesis: Studies from large animals. J. Endocrinol. 2018, 237, R99–R115. [Google Scholar] [CrossRef] [Green Version]
- Hilse, K.E.; Kalinovich, A.V.; Rupprecht, A.; Smorodchenko, A.; Zeitz, U.; Staniek, K.; Erben, R.G.; Pohl, E.E. The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue. Biochim. Biophys. Acta 2016, 1857, 72–78. [Google Scholar] [CrossRef] [Green Version]
- Pohl, E.E.; Rupprecht, A.; Macher, G.; Hilse, K.E. Important trends in UCP3 investigation. Front. Physiol. 2019, 10, 470. [Google Scholar] [CrossRef]
- Zanchi, D.; Depoorter, A.; Egloff, L.; Haller, S.; Mählmann, L.; Lang, U.E.; Drewe, J.; Beglinger, C.; Schmidt, A.; Borgwardt, S. The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review. Neurosci. Biobehav. Rev. 2017, 80, 457–475. [Google Scholar] [CrossRef]
- Clerc, P.; Coll Constans, M.G.; Lulka, H.; Broussaud, S.; Guigné, C.; Leung-Theung-Long, S.; Perrin, C.; Knauf, C.; Carpéné, C.; Pénicaud, L.; et al. Involvement of cholecystokinin 2 receptor in food intake regulation: Hyperphagia and increased fat deposition in cholecystokinin 2 receptor-deficient mice. Endocrinology 2007, 148, 1039–1049. [Google Scholar] [CrossRef] [Green Version]
- Chen, H.; Kent, S.; Morris, M.J. Is the CCK2 receptor essential for normal regulation of body weight and adiposity? Eur. J. Neurosci. 2006, 24, 1427–1433. [Google Scholar] [CrossRef]
- Yu, B.; Lv, X.; Su, L.; Li, J.; Yu, Y.; Gu, Q.; Yan, M.; Zhu, Z.; Liu, B. MiR-148a functions as a tumor suppressor by targeting CCK-BR via inactivating STAT3 and Akt in human gastric cancer. PLoS ONE 2016, 11, e0158961. [Google Scholar] [CrossRef] [PubMed]
- Goedeke, L.; Rotllan, N.; Canfrán-Duque, A.; Aranda, J.F.; Ramírez, C.M.; Araldi, E.; Lin, C.S.; Anderson, N.N.; Wagschal, A.; de Cabo, R.; et al. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nat. Med. 2015, 21, 1280–1289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schmitz, G.; Buechler, C. ABCA1: Regulation, trafficking and association with heteromeric proteins. Ann. Med. 2002, 34, 334–347. [Google Scholar] [CrossRef] [PubMed]
- Schmitz, G.; Langmann, T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim. Biophys. Acta 2005, 1735, 1–19. [Google Scholar] [CrossRef] [PubMed]
- He, Y.; Zhang, L.; Li, Z.; Gao, H.; Yue, Z.; Liu, Z.; Liu, X.; Feng, X.; Liu, P. RIP140 triggers foam-cell formation by repressing ABCA1/G1 expression and cholesterol efflux via liver X receptor. FEBS Lett. 2015, 589, 455–460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Uccelli, A.; Moretta, L.; Pistoia, V. Mesenchymal stem cells in health and disease. Nat. Rev. Immunol. 2008, 8, 726–736. [Google Scholar] [CrossRef]
- El-Farrash, R.A.; Ali, R.H.; Barakat, N.M. Post-natal bone physiology. Semin. Fetal Neonatal. Med. 2020, 25, 101077. [Google Scholar] [CrossRef]
- Katsimbri, P. The biology of normal bone remodelling. Eur. J. Cancer Care 2017, 26, 6. [Google Scholar] [CrossRef]
- Yang, Y.; Wu, F.; Dwyer, T.; Antony, B.; Winzenberg, T.; Jones, G. Associations of breastfeeding, maternal smoking, and birth weight with bone density and microarchitecture in young adulthood: A 25-year birth-cohort study. J. Bone Miner. Res. 2020, 35, 1652–1659. [Google Scholar] [CrossRef]
- Behera, J.; Tyagi, N. Exosomes: Mediators of bone diseases, protection, and therapeutics potential. Oncoscience 2018, 5, 181–195. [Google Scholar] [CrossRef] [Green Version]
- Qin, Y.; Sun, R.; Wu, C.; Wang, L.; Zhang, C. Exosome: A novel approach to stimulate bone regeneration through regulation of osteogenesis and angiogenesis. Int. J. Mol. Sci. 2016, 17, 712. [Google Scholar] [CrossRef]
- Liu, M.; Sun, Y.; Zhang, Q. Emerging role of extracellular vesicles in bone remodeling. J. Dent. Res. 2018, 97, 859–868. [Google Scholar] [CrossRef]
- Pethő, A.; Chen, Y.; George, A. Exosomes in extracellular matrix bone biology. Curr. Osteoporos. Rep. 2018, 16, 58–64. [Google Scholar] [CrossRef]
- Huang, X.; Xiong, X.; Liu, J.; Zhao, Z.; Cen, X. MicroRNAs-containing extracellular vesicles in bone remodeling: An emerging frontier. Life Sci. 2020, 254, 117809. [Google Scholar] [CrossRef]
- Blank, V.; Andrews, N.C. The Maf transcription factors: Regulators of differentiation. Trends Biochem. Sci. 1997, 22, 437–441. [Google Scholar] [CrossRef]
- Nishikawa, K.; Nakashima, T.; Takeda, S.; Isogai, M.; Hamada, M.; Kimura, A.; Kodama, T.; Yamaguchi, A.; Owen, M.J.; Takahashi, S.; et al. Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation. J. Clin. Invest. 2010, 120, 3455–3465. [Google Scholar] [CrossRef] [Green Version]
- Cheng, P.; Chen, C.; He, H.B.; Hu, R.; Zhou, H.D.; Xie, H.; Zhu, W.; Dai, R.C.; Wu, X.P.; Liao, E.Y.; et al. miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B. J. Bone Miner. Res. 2013, 28, 1180–1190. [Google Scholar] [CrossRef]
- Oliveira, M.C.; Di Ceglie, I.; Arntz, O.J.; van den Berg, W.B.; van den Hoogen, F.H.; Ferreira, A.V.; van Lent, P.L.; van de Loo, F.A. Milk-derived nanoparticle fraction promotes the formation of small osteoclasts but reduces bone resorption. J. Cell. Physiol. 2017, 232, 225–233. [Google Scholar] [CrossRef]
- Kelch, S.; Balmayor, E.R.; Seeliger, C.; Vester, H.; Kirschke, J.S.; van Griensven, M. miRNAs in bone tissue correlate to bone mineral density and circulating miRNAs are gender independent in osteoporotic patients. Sci. Rep. 2017, 7, 15861. [Google Scholar] [CrossRef]
- Oliveira, M.C.; Arntz, O.J.; Blaney Davidson, E.N.; van Lent, P.L.; Koenders, M.I.; van der Kraan, P.M.; van den Berg, W.B.; Ferreira, A.V.; van de Loo, F.A. Milk extracellular vesicles accelerate osteoblastogenesis but impair bone matrix formation. J. Nutr. Biochem. 2016, 30, 74–84. [Google Scholar] [CrossRef]
- Oliveira, M.C.; Pieters, B.C.H.; Guimarães, P.B.; Duffles, L.F.; Heredia, J.E.; Silveira, A.L.M.; Oliveira, A.C.C.; Teixeira, M.M.; Ferreira, A.V.M.; Silva, T.A.; et al. Bovine milk extracellular vesicles are osteoprotective by increasing osteocyte numbers and targeting RANKL/OPG system in experimental models of bone loss. Front. Bioeng. Biotechnol. 2020, 8, 891. [Google Scholar] [CrossRef]
- Yun, B.; Maburutse, B.E.; Kang, M.; Park, M.R.; Park, D.J.; Kim, Y.; Oh, S. Short communication: Dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model. J. Dairy Sci. 2020, 103, 7752–7760. [Google Scholar] [CrossRef]
- Lee, B.; Iwaniec, U.T.; Turner, R.T.; Lin, Y.W.; Clarke, B.L.; Gingery, A.; Wei, L.N. RIP140 in monocytes/macrophages regulates osteoclast differentiation and bone homeostasis. JCI Insight 2017, 2, e90517. [Google Scholar] [CrossRef] [Green Version]
- Klein-Nulend, J.; Bacabac, R.G.; Bakker, A.D. Mechanical loading and how it affects bone cells: The role of the osteocyte cytoskeleton in maintaining our skeleton. Eur. Cell Mater. 2012, 24, 278–291. [Google Scholar] [CrossRef]
- Walker, E.C.; Truong, K.; McGregor, N.E.; Poulton, I.J.; Isojima, T.; Gooi, J.H.; Martin, T.J.; Sims, N.A. Cortical bone maturation in mice requires SOCS3 suppression of gp130/STAT3 signalling in osteocytes. eLife 2020, 9, e56666. [Google Scholar] [CrossRef]
- Kylmaoja, E.; Nakamura, M.; Tuukkanen, J. Osteoclasts and remodeling based bone formation. Curr. Stem Cell Res. Ther. 2016, 11, 626–633. [Google Scholar] [CrossRef]
- Zempleni, J.; US Department of Agriculture. Milk Findings May Help Infants Worldwide. Available online: https://www.usda.gov/media/blog/2020/06/01/milk-findings-may-help-infants-worldwide (accessed on 10 May 2021).
- Li, Y.; Nguyen, D.N.; de Waard, M.; Christensen, L.; Zhou, P.; Jiang, P.; Sun, J.; Bojesen, A.M.; Lauridsen, C.; Lykkesfeldt, J.; et al. Pasteurization procedures for donor human milk affect body growth, intestinal structure, and resistance against bacterial infections in preterm pigs. J. Nutr. 2017, 147, 1121–1130. [Google Scholar] [CrossRef] [Green Version]
- Sun, H.; Cao, Y.; Han, S.; Cheng, R.; Liu, L.; Liu, J.; Xia, S.; Zhang, J.; Li, Z.; Cheng, X.; et al. A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother’s own milk for preterm infants in the NICU. Trials 2020, 21, 170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oliveira, M.M.; Aragon, D.C.; Bomfim, V.S.; Trevilato, T.M.B.; Alves, L.G.; Heck, A.R.; Martinez, F.E.; Camelo, J.S., Jr. Development of a human milk concentrate with human milk lyophilizate for feeding very low birth weight preterm infants: A preclinical experimental study. PLoS ONE 2019, 14, e0210999. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hahn, W.H.; Kim, J.; Song, S.; Park, S.; Kang, N.M. The human milk oligosaccharides are not affected by pasteurization and freeze-drying. J. Matern. Fetal Neonatal Med. 2019, 32, 985–991. [Google Scholar] [CrossRef] [PubMed]
- Hahn, W.H.; Bae, S.P.; Song, S.; Park, S.; Lee, J.; Seo, J.B.; Kang, N.M. The freeze-drying does not influence the proteomic profiles of human milk. J. Matern. Fetal Neonatal Med. 2020, 33, 2069–2074. [Google Scholar] [CrossRef]
- Charoenviriyakul, C.; Takahashi, Y.; Nishikawa, M.; Takakura, Y. Preservation of exosomes at room temperature using lyophilization. Int. J. Pharm. 2018, 553, 1–7. [Google Scholar] [CrossRef]
- Zhang, Y.; Bi, J.; Huang, J.; Tang, Y.; Du, S.; Li, P. Exosome: A review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications. Int. J. Nanomed. 2020, 15, 6917–6934. [Google Scholar] [CrossRef]
- Stephen, B.J.; Pareek, N.; Saeed, M.; Kausar, M.A.; Rahman, S.; Datta, M. Xeno-miRNA in maternal-infant immune crosstalk: An aid to disease alleviation. Front. Immunol. 2020, 11, 404. [Google Scholar] [CrossRef] [Green Version]
- Marriott, M.; Schoenthal, L. An experimental study of the use of unsweetened evaporated milk for the preparation of infant feeding formulas. Arch. Pediatr. 1929, 46, 135–148. [Google Scholar]
- Bryder, L. From breast to bottle: A history of modern infant feeding. Endeavour 2009, 33, 54–59. [Google Scholar] [CrossRef]
- Koletzko, B.; von Kries, R.; Closa, R.; Escribano, J.; Scaglioni, S.; Giovannini, M.; Beyer, J.; Demmelmair, H.; Gruszfeld, D.; Dobrzanska, A.; et al. Lower protein in infant formula is associated with lower weight up to age 2 y: A randomized clinical trial. Am. J. Clin. Nutr. 2009, 89, 1836–1845. [Google Scholar]
- Weber, M.; Grote, V.; Closa-Monasterolo, R.; Escribano, J.; Langhendries, J.P.; Dain, E.; Giovannini, M.; Verduci, E.; Gruszfeld, D.; Socha, P.; et al. Lower protein content in infant formula reduces BMI and obesity risk at school age: Follow-up of a randomized trial. Am. J. Clin. Nutr. 2014, 99, 1041–1051. [Google Scholar] [CrossRef]
- Patro-Gołąb, B.; Zalewski, B.M.; Kołodziej, M.; Kouwenhoven, S.; Poston, L.; Godfrey, K.M.; Koletzko, B.; van Goudoever, J.B.; Szajewska, H. Nutritional interventions or exposures in infants and children aged up to 3 years and their effects on subsequent risk of overweight, obesity and body fat: A systematic review of systematic reviews. Obes. Rev. 2016, 17, 1245–1257. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C. Excessive leucine-mTORC1-signalling of cow milk-based infant formula: The missing link to understand early childhood obesity. J. Obes. 2012, 2012, 197653. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C. The potential mechanistic link between allergy and obesity development and infant formula feeding. Allergy Asthma Clin. Immunol. 2014, 10, 37. [Google Scholar] [CrossRef] [Green Version]
- Capuco, A.V.; Akers, R.M. The origin and evolution of lactation. J. Biol. 2009, 8, 37. [Google Scholar] [CrossRef] [Green Version]
- King, F.T. Feeding and Care of Baby; Macmillan: London, UK, 1913; pp. 3, 17, 43. [Google Scholar]
- Leung, A.K.; Sauve, R.S. Breast is best for babies. J. Natl. Med. Assoc. 2005, 97, 1010–1019. [Google Scholar]
Model | MEX Source | Insulting Agents | Biological Effects | References |
---|---|---|---|---|
IEC-6 cells | Human | H2O2 | Increased cell viability; protection from oxidative stress | [231] |
IEC-6 | Yak, Cow | Hypoxia | Yak-MEX increased survival of IEC-6 cells compared with bovine-MEX; yak-MEX promote oxygen-sensitive prolyl hydroxylase (PHD)-1 expression and decrease HIF-α, VEGF and p53 | [72] |
IEC | Porcine | LPS | Decreased LPS-induced TLR4/NF-κB signaling pathway activation; reduced LPS-induced apoptosis via the p53 pathway | [162] |
IEC murine intestine | Porcine | Deoxynivalenol | Up-regulation of miRNA-181a, miRNA-30c, miRNA-365-5p and miRNA-769-3p in IPEC-J2 cells; suppression of p53 pathway; increased proliferation and TJs; inhibition of apoptosis | [85] |
Premature Sprague–Dawley rat pups; IEC-6 cells | Human | Asphyxia, hypothermia, hypercaloric feed, hypoxia | Decrease in histological NEC grade; increased IEC cell proliferation; decreased apoptosis of IEC | [232] |
Prominin-1+ ISCs of small intestines of neonatal rat | Human | H2O2 | Increase in ISC viability; increased expression of LRG5, axin2, c-myc, cyclin D1, HES1, DII1, DII4 | [77] |
LS174T human colonic cells; C57BL/6 mice | Bovine | Hypoxia, hyperosmolar formula, LPS | Increased goblet cell numbers and mucin production; Increased expression trefoil factor 3 (TFF3) and mucin 2 (MUC2). Enhanced the expression of glucose-regulated protein 94 (GRP94) | [47] |
C57BL/6J mice | Bovine | Dextran sulfate sodium | Decreased inflammation through the down-regulation of colitis-associated miRNAs, especially miRNA-125b, associated with a higher expression of the NF-κB inhibitor TNFAIP3 | [84] |
Newborn Sprague–Dawley rat pups; human intestinal epithelial FHC | Human, term/preterm | Hypoxia formula | Preterm MEX significantly enhanced proliferation and migration of IECs compared with term MEX | [233] |
Intestinal organoids; C57BL/6 mice pups | Human | LPS | Decreased expression of TNF-α and TLR4 | [163] |
Balb/c mice | Human | Dextran sulfate sodium | MEX attenuated the severity of colitis induced by DSS and statistically reduced the histopathological scoring grade and shortening of the colon; reduced expression of IL-6, TNF-α, DNMT1 and DNMT3; up-regulation of TGF-β | [148] |
Mdr1a−/− mice (5 weeks old) | Bovine | 60% MEX-deficient diet | Higher degree of intestinal lesions; deficiency of miRNA-200a-3p targeting Cxcl9 mRNA | [234] |
Intestine of kindlin 2 knockout mice | Bovine | Kindlin 2 knockout | Decrease in macroscopic colitis score in MEX-treated mice compared with untreated mice | [235] |
Intestinal organoids of C57BL/6 mouse pups | Human | Hypoxia formula, LPS | Decreased IL-6 mRNA expression; decreased injury score and MPO activity; increase in goblet cell number and MUC2 mRNA expression | [92] |
miRNA-148a 3p Target Genes | Potential Functional Outcomes During Breastfeeding |
---|---|
PRKAA1 | Inhibition of AMPK; suppression of pancreatic β-cell activation; increased IEC-and β-cell mTORC1 activity with IEC and β-cell proliferation |
PRKAG2 | Inhibition of AMPK; suppression of β-cell activation; increased IEC and β-cell mTORC1 activity with IEC- and βcell proliferation |
PPARGC1B | Inhibition of PCG-1β; Reduced mitochondrial function |
UCP3 | Reduced fatty acid β-oxidation and energy expenditure |
CCK2R | Reduced satiety signals increasing milk/food intake |
MAFB | Increased osteoclastogenesis |
LDLR | Reduced hepatic LDL cholesterol uptake |
ABCA1 | Reduced HDL-mediated reverse cholesterol transport |
COL1A1 | Reduced collagen I synthesis |
IL6ST (GP130) | Reduced expression of GP130 resulting in attenuated IL-6 signaling, increased cortical bone maturation |
IKBKA | Inhibition of IκB kinase α and NF-κB signaling, suppression of inflammation |
IKBKB | Inhibition of IκB kinase β and NF-κB signaling, suppression of inflammation |
CAMK2A | Inhibition of calcium/calmodulin-dependent protein kinase IIα and downstream TLR4 signaling |
DNMT1 | Inhibition of DNA methyltransferase 1 increasing epigenetic expression of developmental genes (INS, IGF1; SNCA, FOXP3) and suppression of RIP140 expression and RIP140-dependent nuclear receptors and transcription factors such as PGC-1α |
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Melnik, B.C.; Stremmel, W.; Weiskirchen, R.; John, S.M.; Schmitz, G. Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development. Biomolecules 2021, 11, 851. https://doi.org/10.3390/biom11060851
Melnik BC, Stremmel W, Weiskirchen R, John SM, Schmitz G. Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development. Biomolecules. 2021; 11(6):851. https://doi.org/10.3390/biom11060851
Chicago/Turabian StyleMelnik, Bodo C., Wolfgang Stremmel, Ralf Weiskirchen, Swen Malte John, and Gerd Schmitz. 2021. "Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development" Biomolecules 11, no. 6: 851. https://doi.org/10.3390/biom11060851
APA StyleMelnik, B. C., Stremmel, W., Weiskirchen, R., John, S. M., & Schmitz, G. (2021). Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development. Biomolecules, 11(6), 851. https://doi.org/10.3390/biom11060851