An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases
Abstract
:1. Introduction
1.1. Biological Role and Components of EVs
1.2. Classification of EVs
1.3. Possible Role for Extracellular Vesicles in Gut Maturation
1.3.1. EVs of Bacterial Origin
1.3.2. EVs of Immune System Origin
1.3.3. EVs of Maternal Milk Origin
2. Extracellular Vesicles in the Pathogenesis of IBD
2.1. The Role of EVs in Maintaining the Gut Integrity
2.1.1. Transforming Growth Factor β (TGF-β)
2.1.2. Annexin-1 (ANXA1)
2.1.3. MicroRNAs (miRNAs)
2.1.4. Human Proteins Related to Oxidative Antimicrobial Activities
Extracellular Vesicles | Role in the Pathogenesis of IBD |
---|---|
TGF-β | • EVs with TGF-β1-dependent immunosuppressive activity are released by IECs [63]. |
• EVs with TGF-β1-dependent may lead to reduction inflammation indices through the induction of regulatory T-cells and immunosuppressive dendritic cells [63]. | |
ANXA1 | • ANXA1-deficiency may exhibit impaired clinical and histopathologic recovery following an inflammatory state [64]. |
• ANXA1 may be released as a component of EVs derived from intestinal epithelium and it may activate wound repair circuits [65]. | |
• ANXA1-containing EVs can potentially be used as a biomarker of intestinal inflammation [65]. | |
miRNAs | • MiRNA contained in EVs may affect cell cycle control, cell differentiation and apoptosis [68]. |
• MiRNA can act as agonists of the single-stranded RNA-binding TLRs [69]. | |
• MiRNAs can enhance inflammatory processes (increase secretion of TNF and IL 6) [70]. | |
• The maintenance of gut homeostasis via modification of the PTEN/PI3K/Akt signaling pathway [73,74]. | |
• MiR-29 has been shown to modify pro-inflammatory cytokine release and scavenger-receptor expression by targeting LPL in ox LDL-stimulated DCs [75] | |
• MiR-223 can act as a mediator of the IL923 pathway which suppresses claudin-8 [74]. | |
• Acquisition of miR-223 into IECs downregulates the expression of TJ-related proteins ZO-1, occludin, and claudin-8 [78]. | |
Human proteins related to oxidative antimicrobial activities | • Host defense proteins, including those which produce reactive oxidants are correlated with functional alterations in the microbiota of pediatric IBD patients [80]. |
2.2. The Role of EVs in the Regulation of the Gut Immune System
2.2.1. EVs of Intestinal Epithelial Cell (IEC) Origin
2.2.2. EVs of Immune System Cell Origin
2.2.3. EVs of Bacterial Origin
3. Potential of EVs in Clinical Practice
3.1. Usage of EVs in Treatment
3.1.1. Neonatal NEC
3.1.2. IBD
3.2. The Usage of EVs as Biomarkers
4. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Potential Therapeutic Effect | Mechanism/Therapeutic Factor | Reference |
---|---|---|
Decreasing the release of EV and miRNA-related proteins | Inhibition of VPS4 in HEK293 cells | [111] |
The control of EV secretion | Suppression of proteins involved in the docking and fusion of EVs with the plasma membrane | [112] |
Direct targeting of specific EV cargo components | Inhibition or silencing of miR-21 | [58,113] |
Protective effects on DSS-induced colitis | M2b macrophage-derived EVs mainly mediated by the CC chemokine 1 (CCL1)/CCR8 axis | [114] |
Mobilization of molecules with epithelial repair properties | ANXA1 | [65] |
Reduction in pro-inflammatory cytokines, decreased mucosal inflammatory infiltration, reduced mucosal damage | Nippostrongylus Brasiliensis—derived EVs | [115] |
Preventing colon damage | Schistosoma japonicum soluble egg antigen-treated EVs | [116] |
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Filip, R. An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases. Cells 2021, 10, 3202. https://doi.org/10.3390/cells10113202
Filip R. An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases. Cells. 2021; 10(11):3202. https://doi.org/10.3390/cells10113202
Chicago/Turabian StyleFilip, Rafał. 2021. "An Update on the Role of Extracellular Vesicles in the Pathogenesis of Necrotizing Enterocolitis and Inflammatory Bowel Diseases" Cells 10, no. 11: 3202. https://doi.org/10.3390/cells10113202