Mesenchymal cell-derived exosomes and miR-29a-3p mitigate renal fibrosis and vascular rarefaction after renal ischemia reperfusion injury

BACKGROUND: Renal fibrosis and vascular rarefaction are significant complications of ischemia/reperfusion (I/R) injury. Human umbilical cord mesenchymal cell-derived exosomes (hucMSC-exos) have shown potential in mitigating these conditions. This study investigates the role of miR-29a-3p in exosomes and its therapeutic effects on I/R-induced renal damage. METHODS: Male C57BL/6 mice were subjected to unilateral renal ischemia for 28 min followed by reperfusion. Exosomes and miR-29a-3p mimics/inhibitors were injected into the mice. Renal function, histological analysis, and molecular assays were performed to evaluate fibrosis and vascular integrity. RESULTS: Exosome treatment significantly improved renal function and reduced fibrosis and vascular rarefaction post-I/R. MiR-29a-3p was highly expressed in hucMSC-exos but reduced in renal fibrosis models. MiR-29a-3p mimic reduced, while its inhibitor exacerbated I/R-induced renal fibrosis and vascular rarefaction. Collagen I and TNFR1 were identified as direct targets of miR-29a-3p in fibroblasts and endothelial cells, respectively. Exosomes overexpressing miR-29a-3p provided superior protection compared to unmodified hucMSC-exos. CONCLUSION: HucMSC-exos, particularly those overexpressing miR-29a-3p, have potent therapeutic effects against renal fibrosis and vascular rarefaction post-I/R. MiR-29a-3p targets TNFR1 and collagen I, highlighting its potential in renal fibrosis therapy.