miR-30a Negatively Regulates TGF-β1–Induced Epithelial-Mesenchymal Transition and Peritoneal Fibrosis by Targeting Snai1

Abstract

Although epithelial-mesenchymal transition (EMT) and the subsequent development of peritoneal fibrosis are key processes leading to the peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unclear. In the present study, we found that miR-30a was significantly down-regulated in peritoneal tissues, with progressive fibrosis in patients with continuous ambulatory peritoneal dialysis and in a rat model of PD. In vitro, transforming growth factor (TGF)-β1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in both human and rat peritoneal mesothelial cells, was associated with down-regulation of miR-30a but up-regulation of Snai1, suggesting a close link between miR-30a and Snai1 in TGF-β1-induced peritoneal fibrosis. It was further demonstrated in vitro that miR-30a was able to bind the 3' untranslated region of Snai1 and overexpression of miR-30a blocked TGF-β1-induced up-regulation of Snai1 and, therefore, inhibited EMT and collagen expression. To determine the functional role of miR-30a, we overexpressed miR-30a in the peritoneal tissue in a rat model of PD and found that overexpression of miR-30a blocked both Snai1 and EMT and inhibited peritoneal fibrosis, with improvement of peritoneal dysfunction. In conclusion, miR-30a negatively regulates Snai1-mediated EMT during peritoneal fibrosis in vitro and in vivo. Blockade of peritoneal fibrosis by overexpressing miR-30a in a rat model of PD reveals a therapeutic potential of miR-30a for peritoneal fibrosis associated with PD.

Myofibroblastic Conversion and Regeneration of Mesothelial Cells in Peritoneal and Liver Fibrosis

“…19,30 In TGF-beinduced MMT, SNAIL1 was shown to down-regulate CDH1 expression and thereby induce MMT, similar to the mechanism of cancer metastasis. 20,30,33 However, we could not detect CDH1 expression in either peritoneal or liver MCs by immunohistochemistry in mice. 12 Cultured MCs express Snai1 at a low level (data not shown).…”

MiR-30b is involved in methylglyoxal-induced epithelial-mesenchymal transition of peritoneal mesothelial cells in rats

“…There are different viewpoints about the relationship between the miR-30 family and the EMT of PMCs. A recent paper reported that miR-30a negatively regulated TGF-β1-induced EMT and peritoneal fibrosis by targeting Snai1 [27]. MGO in the present study and TGF-β1 are two different regulators that induced changes in the peritoneal membrane [13,28].…”

MicroRNA-29b inhibits peritoneal fibrosis in a mouse model of peritoneal dialysis

“…To achieve Dox-induced transgene expression, pTRE 2 -miR-29b/pTRE 2 -hygro and pEFpuro-p-Tet-on were co-transfected into the abdominal cavity via an ultrasound-microbubble delivery system as described previously with some modifications. 24,25 Briefly, a mixture of plasmids (pTRE 2 -miR-29b or pTRE 2 -hygro EV) and Sonovue (Bracco Diagnostics, Princeton, NJ, USA) was prepared with 1:1 vol/vol ratio. Then the mixed solution containing 200 mg of designated plasmids in total volume of 1 ml was immediately injected into the peritoneal cavity.…”