Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats. Academic Article uri icon

abstract

  • BACKGROUND: 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. AIMS: We evaluated whether taurocholic acid (TC) can prevent HAL-induced cholangiocyte damage via the alteration of VEGFR-2 and/or VEGF-A expression. METHODS: 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. RESULTS: 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. CONCLUSION: TC prevented HAL-induced biliary damage by upregulation of VEGF-A expression.

published proceedings

  • Dig Liver Dis

author list (cited authors)

  • Glaser, S., Onori, P., Gaudio, E., Ueno, Y., Pannarale, L., Franchitto, A., ... Alpini, G

citation count

  • 14

complete list of authors

  • Glaser, Shannon||Onori, Paolo||Gaudio, Eugenio||Ueno, Yoshiyuki||Pannarale, Luigi||Franchitto, Antonio||Francis, Heather||Mancinelli, Romina||Carpino, Guido||Venter, Julie||White, Mellanie||Kopriva, Shelley||Vetuschi, Antonella||Sferra, Roberta||Alpini, Gianfranco

publication date

  • March 2010