title: 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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Man
authors.initials: M
authors.lastname: Yang
authors.forename: Huiyao
authors.initials: H
authors.lastname: Lan
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C556157:MIRN30 microRNA, rat; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; C000604450:Snai2 protein, rat; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1