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Transforming growth factor‐β1 and mannose 6‐phosphate/insulin‐like growth factor‐II receptor expression during intrahepatic bile duct hyperplasia and biliary fibrosis in the rat
Author(s) -
Saperstein Lawrence A.,
Jirtle Randy L.,
Farouk Marwan,
Thompson Hugh J.,
Chung Kyung S.,
Meyers William C.
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840190220
Subject(s) - medicine , endocrinology , growth factor , bile duct , biology , mannose 6 phosphate , transforming growth factor , intrahepatic bile ducts , receptor
These studies investigate the role of transforming growth factor‐β1, a potent inhibitor of epithelial cell proliferation and stimulator of extracellular matrix biosynthesis, during intrahepatic bile duct hyperplasia and biliary fibrosis. These pathogenic responses were induced in rats by common bile duct ligation. Bile duct cell replication, measured by the bromodeoxyuridine labeling index, was significantly increased 24 hr after common bile duct ligation. This response diminished to baseline by 1 wk. Liver collagen content, determined by quantification of hydroxyproline, was increased significantly after 1 wk of common bile duct ligation, and by 4 wk was increased by a factor of 4. Immunohistochem‐istry revealed low levels of TGF‐β1 in normal intrahepatic bile duct epithelium. In contrast, the bile duct epithelium in bile duct–ligated rats stained strongly positive for transforming growth factor‐β1 at 1 and 4 wk after ligation. These results suggest that transforming growth factor‐β1 may play a role in both the termination of the bile duct epithelial cell proliferative response and the induction of fibrogenesis after common bile duct ligation. In addition, the mannose 6‐phosphate/insulin‐like growth factor II receptor was up‐regulated in hyperplastic bile duct epithelium 1 and 4 wk after ligation. Because the mannose 6‐phosphate/insulin‐like growth factor‐II receptor has been shown to facilitate the proteolytic activation of transforming growth factor‐β1, these results suggest that the bile duct epithelium may also be involved in the activation of transforming growth factor‐β1. (Hepatology 1994;19:412–417).