The expression of epithelial-mesenchymal transition-related proteins in biliary epithelial cells is associated with liver fibrosis in biliary atresia

Pediatr Res. 2015 Feb;77(2):310-5. doi: 10.1038/pr.2014.181. Epub 2014 Nov 19.

Abstract

Background: The epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of liver fibrosis. The miR-200 family has been shown to inhibit EMT.

Methods: Liver fibrosis levels were assessed with Masson's trichrome staining of liver samples obtained from biliary atresia (BA) patients. The expressions of cytokeratin-7 (CK-7) and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical and immunofluorescent staining. EMTs were induced by transforming growth factor (TGF)-β1 in human biliary epithelial cells (BECs) in vitro.

Results: We showed that the EMT-related proteins CK-7 and α-SMA colocalized to the intrahepatic BECs in the liver sections of patients with BA. The level of α-SMA expression was related to liver fibrosis stage in BA. EMT in primary human intrahepatic BECs was induced by TGF-β1 in vitro. miR-200b is one member of the miR-200 family and significantly inhibited TGF-β1-mediated EMT in BECs.

Conclusion: Together, these data suggest that the occurrence of EMT in BECs might contribute to BA fibrosis. miR-200b significantly affects the development and progression of TGF-β1-dependent EMT and fibrosis in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Bile Ducts / cytology
  • Biliary Atresia / complications*
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / physiology*
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Keratin-7 / metabolism*
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / physiopathology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Keratin-7
  • Transforming Growth Factor beta1