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.

DOI: 10.1007/s11010-017-2988-y

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Cite this paper

@article{Xu2017TGF1miR200aPTENIE, title={TGF-β1-miR-200a-PTEN induces epithelial–mesenchymal transition and fibrosis of pancreatic stellate cells}, author={Min Xu and Guoying Wang and Hailang Zhou and Jing Cai and Ping Li and Meng Zhou and Ying Lu and Xiaomeng Jiang and Hongmei Huang and Youli Zhang and Ai-hua Gong}, journal={Molecular and Cellular Biochemistry}, year={2017}, volume={431}, pages={161-168} }