Curcumin mitigates the epithelial-to-mesenchymal transition in biliary epithelial cells through upregulating CD109 expression

Drug Dev Res. 2019 Nov;80(7):992-999. doi: 10.1002/ddr.21580. Epub 2019 Aug 12.

Abstract

Biliary epithelial cells (BECs) can secrete bile and the epithelial-to-mesenchymal transition (EMT) of BECs can cause fibrosis or damage interlobular bile ducts, leading to chronic cholangiopathies, such as primary biliary cholangitis (PBC). Transforming growth factor-β1 (TGF-β1) is a potent inducer of the EMT while curcumin, a diarylheptanoid, can inhibit the EMT of hepatocytes in many liver diseases. However, the protection and underlying mechanisms of curcumin against the EMT of BECs have not been clarified. Herein, we show that curcumin treatment significantly mitigates the EMT of BECs in vitro and in vivo. Mechanistically, curcumin significantly attenuated the TGF-β1-induced Smad and Hedgehog signaling, and upregulated CD109 expression in BECs. Collectively, these findings highlighted the therapeutic potential of curcumin to counteract the EMT process in PBC.

Keywords: CD109; TGF-β1; curcumin; epithelial-to-mesenchymal transition; primary biliary cholangitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • GPI-Linked Proteins / biosynthesis
  • Hedgehog Proteins / metabolism
  • Humans
  • Mice
  • Neoplasm Proteins / biosynthesis*
  • Smad2 Protein / biosynthesis
  • Smad3 Protein / biosynthesis
  • Smad7 Protein / biosynthesis
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / pharmacology
  • Up-Regulation / drug effects*

Substances

  • Antigens, CD
  • CD109 protein, human
  • GPI-Linked Proteins
  • Hedgehog Proteins
  • Neoplasm Proteins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD7 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Smad7 Protein
  • Transforming Growth Factor beta1
  • Curcumin