Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis.
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.
Sasaki
Motoko
M
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan. m8sasaki@med.kanazawa-u.ac.jp
Ikeda
Hiroko
H
Kataoka
Hiroaki
H
Nakanuma
Yasuni
Y
D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C109149:SPINT1 protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C081092:HGF activator; D012697:Serine Endopeptidases