Mesenchymal stem cell-derived exosome miR-21-3p prevents renal fibrosis

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. Mesenchymal stem cells (MSCs) exerts its therapeutic effect mainly through paracrine effects, such as exosome, to change the cellular microenvironment. Here, we explore the function of exosome derived MSCs in renal fibrosis. Methods: : UUO model was constructed to simulate renal fibrosis in mice. Heat map and RT-PCR were used to explore the differential expression of miRNAs. RT-PCR and western blot were performed to detect the expression levels of fibrosis-associated genes and proteins in vivo and vitro. Transmission electron microscope and particle size detection were used to confirm the exosome construct. Then we forced expression of miR-21-3p in MSCs and isolated the exosomes. Then the fibrosis-associated genes and proteins were explored after exosomes injection. 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). The extractive exosome-miR-21-3p treatment blocked renal fibrosis in UUO mice and alleviated fibrosis in TGF-β1-induced HK-2 cells and renal fibrosis mice. 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.