MiR-34a induces myofibroblast differentiation from renal fibroblasts

BackgroundRenal fibrosis is the common outcome of progressive kidney diseases. To avoid dialysis, the molecular mechanism of renal fibrosis must be explored further. MicroRNAs play key roles in renal fibrosis. MiR-34a is a transcriptional target of p53, which regulates the cell cycle and apoptosis. Previous studies demonstrated that miR-34a promotes renal fibrosis. However, the distinct roles of miR-34a in renal fibrosis have not been fully elucidated. Here, we identified the roles of miR-34a in renal fibrosis.MethodWe first analyzed p53 and miR-34a expression in kidney tissues in s UUO (unilateral ureteral obstruction) mouse model. Then, to confirm the effects of miR-34a in vitro, we transfected a miR-34a mimic into a kidney fibroblast cell line (NRK-49F) and analyzed.ResultsWe found that the expression of p53 and miR-34a was upregulated after UUO. Furthermore, after transfection of the miR-34a mimic into kidney fibroblasts, the expression of alpha-SMA was upregulated dramatically. In addition, alpha-SMA upregulation was greater upon transfection of the miR-34a mimic than upon treatment with TGF-beta 1. Moreover, high expression of Acta2 was maintained despite sufficient removal of the miR-34a mimic by changing the medium 4 times during the 9-day culture. After transfection of the miR-34a mimic into kidney fibroblasts, we did not detect phospho-SMAD2/3 by immunoblotting analysis.ConclusionOur study revealed that miR-34a induces myofibroblast differentiation from renal fibroblasts. Moreover, the miR-34a-induced upregulation of alpha-SMA was independent of the TGF-beta/SMAD signaling pathway. In conclusion, our study indicated that the p53/miR-34a axis promotes the development of renal fibrosis.