Molecular machanisms of cholestasis in a mouse model of chemical induced bile duct injury

Abstract

Chronic cholestasis represents an important couse of biliary fibrosis and cirrhosis. We aimed to characterize hepatobiliary injury and biliary fibrosis in a mouse model of xenobiotic-induced cholangiopahty. Therefore liver morphology, markers of inflammation, proliferation, fibrosis, bile formation and hepatobiliary transporter espression were studied in control diet-fed and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed Swiss albino mice (0,1/ w/w, for 1,4 and 8 weeks). DDC feeding led to induction of VCAM, osteopontin, and TNF- expression in bile duct epithelial cells. This was paralleled by a pronounced percholangitis with significantly increased number of CD11-positive cells, ductular proliferation and proliferation of perductal myofibroblasts leading to a biliary type of fibrosis (hepatic hydroxyproline content 23973 vs. 9216 g liver in controls, p

Date of Award	2006
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Peter Fickert (Supervisor) & Michael Trauner (Supervisor)