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Ischemic injury by hepatic artery ligation (HAL) during obstructive cholestasis induced by bile duct ligation (BDL) results in bile duct damage, which can be prevented by administration of VEGF-A. The potential regulation of VEGF and VEGF receptor expression and secretion by bile acids in BDL with HAL is unknown. We evaluated whether taurocholic acid (TC) can prevent HAL-induced cholangiocyte damage via the alteration of VEGFR-2 and/or VEGF-A expression. Utilizing BDL, BDL+TC, BDL+HAL, BDL+HAL+TC, and BDL+HAL+wortmannin+TC treated rats, we evaluated cholangiocyte apoptosis, proliferation, and secretion as well VEGF-A and VEGFR-2 expression by immunohistochemistry. In vitro, we evaluated the effects of TC on cholangiocyte secretion of VEGF-A and the dependence of TC-induced proliferation on the activity of VEGFR-2. In BDL rats with HAL, chronic feeding of TC prevented HAL-induced loss of bile ducts and HAL-induced decreased cholangiocyte secretion. TC also prevented HAL-inhibited VEGF-A and VEGFR-2 expression in liver sections and HAL-induced circulating VEGF-A levels, which were blocked by wortmannin administration. In vitro, TC stimulated increased VEGF-A secretion by cholangiocytes, which was blocked by wortmannin and stimulated cholangiocyte proliferation that was blocked by VEGFR-2 kinase inhibitor. TC prevented HAL-induced biliary damage by upregulation of VEGF-A expression. Copyright 2010 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.


Shannon Glaser, Paolo Onori, Eugenio Gaudio, Yoshiyuki Ueno, Luigi Pannarale, Antonio Franchitto, Heather Francis, Romina Mancinelli, Guido Carpino, Julie Venter, Mellanie White, Shelley Kopriva, Antonella Vetuschi, Roberta Sferra, Gianfranco Alpini. Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2010 Oct;42(10):709-17

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PMID: 20303838

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