Site-characteristic expression and induction of trefoil factor family 1, 2 and 3 and malignant brain tumor-1 in normal and diseased intrahepatic bile ducts relates to biliary pathophysiology.
OBJECTIVE
Trefoil factor family (TFF)1,2,3 are involved in a homeostasis/repair process of mucosal epithelia. In this study, the significance of TFF family and deleted in the malignant brain tumor-1 (DMBT1), a putative receptor of TFF2, in the intrahepatic biliary tree was investigated in normal and diseased livers.


METHODS
Expression of TFF1,2,3 and DMBT1 were examined immunohistochemically in primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), extrahepatic biliary obstruction (EBO), and normal livers.


RESULTS
In normal livers, TFF1,3 and DMBT1 were infrequently detectable in large and rarely in small bile ducts, respectively. TFF2 was not detectable in large bile ducts. In large bile duct diseases (PSC and EBO), expression of TFF3 and DMBT1 were increased. In small bile duct diseases (PBC and CVH), expression of TFF2/DMBT1 was induced in moderately to severely damaged ducts irrespective of etiology.


CONCLUSIONS
The intrahepatic biliary tree shows a site-characteristic expression and induction of TFF1,2,3 and DMBT1. In large bile ducts, TFF1,3 were constitutively expressed and increased in pathologic bile ducts. In small bile ducts, TFF2/DMBT1 is induced in damaged ducts irrespective of etiologies. However, the cytoprotective/repair property of TFF2/DMBT1 may not be enough to prevent the following bile duct loss in PBC.
Sasaki
Motoko
M
Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Tsuneyama
Koichi
K
Saito
Takahito
T
Kataoka
Hiroaki
H
Mollenhauer
Jan
J
Poustka
Annemarie
A
Nakanuma
Yasuni
Y
D000373:Agglutinins; D001649:Bile Duct Diseases / Q000378:metabolism / Q000503:physiopathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D015209:Cholangitis, Sclerosing / Q000378:metabolism / Q000503:physiopathology; D002779:Cholestasis / Q000378:metabolism / Q000503:physiopathology; D004268:DNA-Binding Proteins; D004066:Digestive System Diseases / Q000378:metabolism / Q000503:physiopathology*; D006521:Hepatitis, Chronic / Q000378:metabolism / Q000503:physiopathology; D006525:Hepatitis, Viral, Human / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000503:physiopathology; D009077:Mucins / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009479:Neuropeptides; D010455:Peptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D011956:Receptors, Cell Surface; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins