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.