The Role Of Mir-200c In Renal Fibrosis And Its Mechanism

Objective:Tubular epithelial-to-mesenchymal transition(EMT)plays pivotal roles in the process of renal fibrosis.miR-200c has been shown to inhibit EMT.Here we show that miR-200c inhibit transforming growth factor-beta(TGF-?1)-induced EMT in tubular cells.However,it remains unclear whether the specific mechanism by which miR-200c functions and whether may play a role by inhibiting the MAPK pathway.Method:This study was based on a renal fibrosis model.In vitro,TGF-?1-induced human renal tubular epithelial cell fibrosis was transfected into miR-200c mimic or miR-200c inhibitor,and fibrosis related indicators were detected by western blot and cell immunofluorescence.The luciferase reporter gene assay confirms the miR-200c target gene and then validates its mechanism in the relevant pathway.In vivo experiments established a unilateral ureteral obstruction(UUO)mouse model and injected the miR-200c agromir tail vein to detect changes in related parameters.Results:In the TGF-?1-induced tubular epithelial cell fibrosis model,after over-expression of miR-200c,the expression of a-SMA decreased,and the expression of E-cadherin was up-regulated.After miR-200c was inhibited,the conclusion was reversed.By luciferase reporter gene detection,MAP3K1 is the target gene of miR200c,and siMAP3K1 can reduce the degree of renal fibrosis.At the same time,we proved that after overexpression or inhibition of miR-200c,the MAPK signaling pathway p-ERK1/2,p-p38 The expressions were reduced or increased,respectively.In addition,by injecting miR-200c agromir into the tail vein of UUO mice,the renal function index was lower than that of UUO mice,the expression of E-cadherin was increased,and the expression of a-SMA was decreased.Conclusion:We suggest that miR-200c could delay the progression of renal fibrosis by inhibiting the MAPK pathway,and miR-200c might constitute novel therapeutic targets in kidney disease.