Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis

Virchows Arch. 2006 Oct;449(4):462-71. doi: 10.1007/s00428-006-0257-7. Epub 2006 Aug 29.

Abstract

The repair system of damaged biliary mucosa was not fully clarified so far in primary biliary cirrhosis (PBC). Given that related factors of the hepatocyte growth factor (HGF) such as HGF activator (HGFA) and HGFA inhibitor type 1 (HAI-1) participate in the repair of injured gastrointestinal mucosa, we investigated the involvement of the HGF/HGFA/HAI-1 system in PBC and control livers. The expression of HGFA, HAI-1, and c-Met was examined in PBC livers (n=24), diseased livers (control, n=30), and normal livers (n=15) by immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction. We examined the expression of HGFA, HAI-1, and c-Met, and the effect of HGF administration on cell proliferation and wound healing, and HAI expression in cultured mouse biliary epithelial cells (BECs). HAI-1 expression was faint in control livers, whereas it was significantly augmented in damaged small bile ducts, bile ductules, and periportal hepatocytes in PBC (p<0.05). HGFA and c-Met were homogeneously expressed in BECs in PBC and control livers. HAI-1 expression was increased at the front of wound healing and the treatment with HGF-enhanced HAI-1 expression, cell proliferation, and wound healing in cultured BECs. HGF/HGFA/HAI-1 system may participate in biliary mucosal repair as reported in gastrointestinal mucosal repair.

MeSH terms

  • Bile Ducts, Intrahepatic / drug effects
  • Bile Ducts, Intrahepatic / metabolism*
  • Bile Ducts, Intrahepatic / pathology
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / pharmacology
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis, Biliary / metabolism*
  • Liver Cirrhosis, Biliary / pathology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Proteinase Inhibitory Proteins, Secretory
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Wound Healing / drug effects

Substances

  • Membrane Glycoproteins
  • Proteinase Inhibitory Proteins, Secretory
  • RNA, Messenger
  • SPINT1 protein, human
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • HGF activator
  • Serine Endopeptidases