Molecular and Cellular Biochemistry

, Volume 431, Issue 1–2, pp 161–168 | Cite as

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


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.


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



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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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


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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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