title: TGF-β1-miR-200a-PTEN induces epithelial-mesenchymal transition and fibrosis of pancreatic stellate cells.
abstract: Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in pancreatic fibrosis is still poorly understood. In this study, we for the first time confirm that miR-200a attenuates TGF-β1-induced pancreatic stellate cells activation and extracellular matrix formation. First, we find that TGF-β1 induces activation and extracellular matrix (ECM) formation in PSCs, and the effects are blocked by the inhibitor of PI3K (LY294002). Furthermore, we identify that miR-200a is down-regulated in TGF-β1-activated PSCs, and up-regulation of miR-200a inhibits PSCs activation induced by TGF-β1. Meanwhile, TGF-β1 inhibits the expression of the epithelial marker E-cadherin, and increases the expression of mesenchymal markers vimentin, and the expression of ECM proteins a-SMA and collagen I, while miR-200a mimic reversed the above effects in PSCs, indicating that miR-200a inhibits TGF-β1-induced activation and epithelial-mesenchymal transition (EMT). In addition, overexpression of miR-200a promotes the expression of PTEN and decreases the expression of matrix proteins and attenuates phosphorylation of Akt and mTOR. Taken together, our study uncovers a novel mechanism that miR-200a attenuates TGF-β1-induced pancreatic stellate cells activation and ECM formation through inhibiting PTEN /Akt/mTOR pathway.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Hailang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China. ahg5@mail.ujs.edu.cn.|Jiangsu University, xuefu 301, Zhenjiang, 212013, Jiangsu Province, China. ahg5@mail.ujs.edu.cn.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
mesh_terms: D000818:Animals; D002867:Chromones / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D002867:Chromones; D035683:MicroRNAs; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1; C555600:MIRN200 microRNA, rat; C508962:Tgfb1 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C487216:Pten protein, rat
keywords: Epithelial–mesenchymal transition; MiR-200a; PTEN/Akt/mTOR pathway; Pancreatic stellate cells; TGF-β1