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

  • Min Xu
  • Guoying Wang
  • Hailang Zhou
  • Jing Cai
  • Ping Li
  • Meng Zhou
  • Ying Lu
  • Xiaomeng Jiang
  • Hongmei Huang
  • Youli Zhang
  • Aihua Gong
Article

DOI: 10.1007/s11010-017-2988-y

Cite this article as:
Xu, M., Wang, G., Zhou, H. et al. Mol Cell Biochem (2017). doi:10.1007/s11010-017-2988-y

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.

Keywords

MiR-200a TGF-β1 Epithelial–mesenchymal transition Pancreatic stellate cells PTEN/Akt/mTOR pathway 

Supplementary material

11010_2017_2988_MOESM1_ESM.tif (384 kb)
Supplementary material 1 (TIF 383 KB)

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Min Xu
    • 1
  • Guoying Wang
    • 1
  • Hailang Zhou
    • 1
  • Jing Cai
    • 1
  • Ping Li
    • 1
  • Meng Zhou
    • 1
  • Ying Lu
    • 1
  • Xiaomeng Jiang
    • 1
  • Hongmei Huang
    • 1
  • Youli Zhang
    • 1
  • Aihua Gong
    • 2
    • 3
  1. 1.Department of Gastroenterology, Affiliated Hospital of Jiangsu UniversityJiangsu UniversityZhenjiangChina
  2. 2.Department of Cell Biology, School of MedicineJiangsu UniversityZhenjiangChina
  3. 3.Jiangsu UniversityZhenjiangChina

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