No abstract

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-β-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-β-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-β-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-β-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.