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TGF-β1-miR-200a-PTEN induces epithelial–mesenchymal transition and fibrosis of pancreatic stellate cells

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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.

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Acknowledgements

This study was supported by Grants from the Natural Science Foundation of Jiangsu Province (BK20131247) and the Research Project of “169 Project” in Zhenjiang City.

Author Contributions

Aihua Gong and Min Xu conceived the idea and designed the experiments. Min Xu, Guoying Wang, and Hailang Zhou analyzed data and wrote the paper, and the other remaining authors collected data. Min Xu and Guoying Wang equally contributed to this work.

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Authors and Affiliations

  1. Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China

    Min Xu, Guoying Wang, Hailang Zhou, Jing Cai, Ping Li, Meng Zhou, Ying Lu, Xiaomeng Jiang, Hongmei Huang & Youli Zhang

  2. Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China

    Aihua Gong

  3. Jiangsu University, xuefu 301, Zhenjiang, 212013, Jiangsu Province, China

    Aihua Gong

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  1. Min Xu
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Correspondence to Aihua Gong.

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Xu, M., Wang, G., Zhou, H. et al. TGF-β1-miR-200a-PTEN induces epithelial–mesenchymal transition and fibrosis of pancreatic stellate cells. Mol Cell Biochem 431, 161–168 (2017). https://doi.org/10.1007/s11010-017-2988-y

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  • DOI: https://doi.org/10.1007/s11010-017-2988-y

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