Mesenchymal Stem Cell-Derived Exosome miR-21-3p Prevents Renal Fibrosis

Abstract

Background: Renal fibrosis is the pathological result of excessive deposition of extracellular matrix (ECM) in the process of chronic kidney disease, but its mechanism is not clear. Preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) can delay the progression of chronic kidney disease (CKD).MSCs exerts its therapeutic effect mainly through paracrine effects, such as exosome, to change the cellular microenvironment. Here, we would explore the function of MSCs derived exosome in renal fibrosis.Materials and Methods: MRNA, microRNAs and proteins carried by exosomes produced by MSCs could save damaged cells by regulating endogenous molecules to regulate apoptosis, inflammation, fibrosis and angiogenesis. Results: In this study, we observed that exogenous miR-21-3p, interacted with smad2, the downstream target of miR-21-3p, which prevented renal fibrosis in UUO mice, and alleviate fibrosis in TGF-β1-induced renal tubular epithelium cells (HK-2). Then we forced expression of miR-21-3p in MSCs and isolated the exosomes. The extractive exosome-miR-21-3p treatment blocked renal fibrosis in UUO mice and alleviated fibrosis in TGF-β1-induced HK-2 cells. Conclusion: Taken together, Overexpression of miR-21-3p prevented CKD-induced renal fibrosis via exosome-mediated miR-21-3p transfer. These results suggest possible therapeutic strategies for using exosome delivery of miR-21-3p to treat complications of CKD.