Exosomes Highlight Future Directions in the Treatment of Acute Kidney Injury
Abstract
:1. Introduction
2. Role of Exosomes of Different Origins in AKI
2.1. Role of Exosomes of MSCs in AKI
2.2. Role of Exosomes from Other Sources in AKI
3. Role of Exosome Content in AKI
3.1. Reparative Effects
3.2. Damaging Effects
4. Exosomes and Their Contents Act as Biomarkers for AKI
5. Engineering Exosomes
5.1. Isolation and Enrichment
5.2. Targeted Therapy
5.3. Exosome Modifications
6. Future Directions
6.1. Accelerating Clinical Translation
6.2. Elucidating Pathways of Reaching the Renal Tubules
6.3. Exosomes and Multi-Omics Studies
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Exo Source | Model | Mechanism | Pathways/Markers | Reference |
---|---|---|---|---|
BMMSC | IRI Rats Mice HK-2 (H/R) | Anti-apoptotic Reduces oxidative stress Anti-inflammatory Promote angiogenesis Inhibits endoplasmic reticulum stress | IL-6, TNF-α, NF-κB IFN-γ ↓ caspase-9, cleaved caspase-3, Bax, and Bcl-2 ↓ BIP miR-149/let-7c/Faslg | [24,54,55] |
BMMSC | UUO Rats | Inhibits fibrosis Epithelial mesenchymal transformation Anti-inflammatory Anti-apoptotic | STAT3 ↓ MMP-9P Colla1,α-SMA ↓ PCNA ↓ | [19] |
BMMSC | Cisp Mice | Anti-apoptotic Reduces DNA damage | Inhibiting p53 | [27] |
SCAP | Cisp NRK-52E | Anti-apoptotic Reduces oxidative stress Anti-inflammatory | NF-κβ, IL-1β, p53 ↓ Bcl-2 ↑ Bax, CASP8, CASP9, and CASP3 ↓ | [31] |
hAEC | IRI mice HK-2 (H/R) | Anti-apoptotic Anti-inflammatory Promote angiogenesis | extracellular matrix growth factor cytokine production, immunomodulation | [33] |
hAEC | Sepsis LPS-treated HUVECs CLP mice | Anti-inflammatory Maintained endothelial cell adhesion junction Mitigating endothelial dysfunction | phosphor-p65, p65, VCAM-1, ZO-1 | [35] |
hAEC | Cisp mice | Anti-inflammatory | TNF-α/MAPK and caspase signaling ↓ | [34] |
ADMSC | IRI | Anti-apoptotic Anti-inflammatory Reduces oxidative stress, DNA damage Promote angiogenesis Inhibits fibrosis Relieves tubular damage | TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2 ↓ NOX-1/NOX-2/oxidized protein ↓ Bax/caspase-3/PARP ↓ Smad3/TGF-β ↓ | [38] |
ADMSC | Sepsis CLP mice LPS HK-2 | Anti-apoptotic Anti-inflammatory Promote angiogenesis Autophagy | SIRT1 TLR9 | [37,39,41] |
ADMSC | Postrenal AKI Cats | Metabolome | carnitine, melibiose, D-Glucosamine, cytidine, dihydroorotic acid, stachyose ↑ | [42] |
USCs | Plasma from AKI patients IRI rats IRI mice HK-2 (H/R) | Anti-inflammatory Inhibits fibrosis Reduces oxidative stress | TRAF6 IRAK1 NF-κB p65 IL10 and TGFβ1 ↑ IFN-γ and IL-1β ↓ | [51,52,53] |
IPSC | IRI HK-2 (H/R) | Reduce renal damage | ERK 1/2 signaling | [50] |
HuMSC | Cisp NRK-52E cells | Promotes TEC proliferation Anti-apoptotic Anti-inflammatory Reduces oxidative stress Promotes mitochondrial fusion Autophagy | fibronectin, α-SMA, GSDMD, caspase-1, IL-1β and NLRP3 ↓ | [56] |
HuMSC | UUO rats | Inhibits fibrosis | CK1δ/β-TRCP inhibited YAP activity | [47] |
HuMSC | IRI rats | Anti-inflammatory Inhibits fibrosis Reduces oxidative stress | [45,46,57] | |
Macrophages | Sepsis CLP mice | Relieves endothelial cell dysfunction Reduces tubular cell apoptosis, pyroptosis | HMGB, VCAM1 ↓ | [56] |
Pericytes | IRI mice | Reduces tubular cell damage Maintain capillary stability | Cadherin APN | [58] |
EPC | Sepsis CLP rats | Anti-inflammatory | RUNX1 ↓ | [59] |
Content | Exo Source | Model | Mechanism | Pathways | Reference |
---|---|---|---|---|---|
miR-199a-3p | BMMSC | IRI mice HK-2 (H/R) | Anti-apoptotic Reduces oxidative stress | Sema3A ↓—ERK, AKT ↑ | [24] |
miR-let-7b-5p | BMMSC | Cisp mice | Anti-apoptotic Reduces DNA damage | p53 ↓—DNA damage and apoptosis pathway activity ↓ | [27] |
miR-1184 | BMMSC | HK-2 by cisp | Anti-apoptotic Anti-inflammatory Break the G1 block | Targeting FOXO4, p27 Kip1 and CDK2 | [66] |
miR-146b | HucMSC | LPS HK-2 CLP mice | Anti-inflammatory | IRAK1 ↓ NF-κB ↓ | [67] |
miR-486-5p | HucMSC | IRI mice | Promotes proliferation angiogenesis | PTEN ↓—Akt phosphorylation | [45] |
miR-486-5p | HucMSC | IRI mice | Anti-apoptotic Anti-inflammatory | protein kinase B ↑ TNF pathway ↓ phosphatase and tensin homolog↓ | [68] |
miR-125b-5p | HucMSC | IRI mice HK-2 (H/R) | Break the G2/M block Anti-apoptotic | P53 ↓—CDK1 and Cyclin B1 ↑ modulation of Bcl-2 and Bax accumulated in proximal tubules by virtue of the VLA-4 and LFA-1 | [46] |
miR-874-3p | HucMSC | UUO mice HK-2 by cisp | Reduce necrosis Promotes mitochondrial fusion | RIPK1 PGAM5 ↓—dephosphorylation of the S637 site of the Drp1 gene | [69] |
miR-342-5p | ADMSC | Sepsis patients with sepsis-associated AKI CLP mice HK-2 by LPS | Enhanced autophagy Anti-inflammatory Reduced BUN and SCr levels | TLR9 ↓—autophagy ↑ BUN, SCr, ↓ | [41] |
miR-216a-5p | USC | IRI rats HK-2 (H/R) | Promote proliferation Angiogenesis | PTEN ↓—Akt phosphorylation | [70] |
miR-146a-5p | USC | IRI rats HK-2 (H/R) | Anti-inflammatory Anti-apoptotic | Target 3′UTR of IRAK1—NF-κB ↓ | [52] |
miR-30a-5p | USCp | Cisp mice HK-2 by cisp | Anti-apoptotic Anti-inflammatory | MAPK8 ↓ | [71] |
miR-93-5p | Macrophage (M2 > M1) | CLP mice TCMK-1 cells by LPS | Renal epithelial cell pyroptosis Anti-inflammatory Anti-apoptotic | TXNIP—pyroptosis in renal epithelial cell | [72] |
miR-590-3p | TEC | AKI patients after cardiac surgery HK-2 (H/R) | Autophagy | miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery Beclin-1 and LC3II ↑ | [53] |
miR-20a-5p | TEC H | HK-2 (H/R) IRI mice | Promotes TEC proliferation, Promotes mitochondrial fusion, Attenuating necrosis | macrophages infiltration ↓ | [73] |
miR-21-5p | ECFC | CLP mice | Anti-inflammatory Promotes proliferation angiogenesis | RUNX1 ↓ | [60] |
miR-486-5p | ECFC | IRI mice | Promotes proliferation angiogenesis | PTEN ↓—Akt phosphorylation | [45] |
miR-93-5p | EPC | HK-2 by LPS CLP mice | Anti-apoptotic Anti-inflammatory | Regulating KDM6BH/3K27me3/TNF-α axis | [74] |
miR-124 | Unknown | CIS mice | Anti-inflammatory | MCP-1 ↑ | [75] |
miR500a3p | Unknown | HK-2 by cisp | Reduce necrosis | RIPK3 and MLKL ↓ | [76,77] |
miR-150-5p | Unknown | HK-2 by LPS LPS mice | Anti-apoptotic Anti-inflammatory and oxidative stress | MEKK3/JNK pathway | [78] |
lncRNA TUG1 | USC | HK-2 (H/R) IRI mice | Reduce Ferroptosis | ACSL4 ↑—TUG1’s repression ↓ miR-494-3p—E-cadherin and TUG1 | [79] [80] |
CCR2 | BMMSC | IRI mice | Inhibits macrophage recruitment activation | Unknown | [81] |
14-3-3z | HucMSC | NRK-52E by cisp Cisp Rats | Autophagy | ATG16L↑ | [82] |
CD26 | TEC | IRI mice | Anti-inflammatory Promotes TEC proliferation | CXCR4, SDF1 ↓ | [83] |
Klotho | USC | AKI rats | Anti-apoptotic Anti-inflammatory Promotes proliferation angiogenesis | fibrosis, monocyte infiltration ↓ SOD1 ↑ | [84] |
Content | Exo Source | Model | Mechanism | Pathways | Reference |
---|---|---|---|---|---|
miR-195a-5p | Macrophage | Cisp mice | Promote TEC apoptosis and damage TEC mitochondria | unknown | [85] |
miR-155 | Macrophage | IRI/cisp mice HK-2 (cisp) NRK-52E (H/R) | Promote TEC damage, promote inflammation limiting the telomeric dysfunction and the genomic DNA damage | TRF1, CDK12 ↓ TCF4/Wnt/β-Catenin | [86,94,95] |
miR-19b-3p | LPS-TEC | Sepsis LPS mice | Promotes inflammation, macrophage 1 polarization | NF-κB/SOCS-1 | [91] |
miR-150-5p | TEC | IRI UIRI rats NRK-52E (H/R) | Activates fibroblasts and promotes fibrosis | suppressor of cytokine signaling 1 to activate fibroblast ↓ | [88] |
miR374b-5p | TEC | IRI mice | Promote Macrophage 1 polarization | Transferring miR-374b-5p | [90] |
miR-709 | PTC | Cisp mice human AKI kidney | Promote TEC apoptosis and mitochondria damage | TFAM ↓ miR-709 in PTCs of patients ↑ | [89] |
miR-23a | TEC H | UUO/IRI mice and TEC | Promotes inflammation Macrophage activation | suppression of the ubiquitin editor A20 | [92] |
miR-30d-5p | Neutrophils mice | Sepsis | Promotes inflammation, macrophage 1 polarization Promotes pyroptosis of macrophages | NLRP3—NF-κB ↑ SOCS-1 and SIRT1 ↓ | [93] |
Circ-FANCA | Sepsis patient LPS-HK2 | Sepsis LPS HK-2 | Promotes inflammation, apoptosis Inhibit proliferation (G0/G1 arrest) | sponging OXSR1 | [96] |
Circ0001818 | Unknown (Serum) | LPS-HK2 | Promote LPS-HK2 damage | miR-136-5p—TXNIP | [97] |
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Zhang, X.; Wang, J.; Zhang, J.; Tan, Y.; Li, Y.; Peng, Z. Exosomes Highlight Future Directions in the Treatment of Acute Kidney Injury. Int. J. Mol. Sci. 2023, 24, 15568. https://doi.org/10.3390/ijms242115568
Zhang X, Wang J, Zhang J, Tan Y, Li Y, Peng Z. Exosomes Highlight Future Directions in the Treatment of Acute Kidney Injury. International Journal of Molecular Sciences. 2023; 24(21):15568. https://doi.org/10.3390/ijms242115568
Chicago/Turabian StyleZhang, Xiaoyu, Jing Wang, Jing Zhang, Yuwei Tan, Yiming Li, and Zhiyong Peng. 2023. "Exosomes Highlight Future Directions in the Treatment of Acute Kidney Injury" International Journal of Molecular Sciences 24, no. 21: 15568. https://doi.org/10.3390/ijms242115568