1. Academic Validation
  2. Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats

Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats

  • Dig Liver Dis. 2010 Oct;42(10):709-17. doi: 10.1016/j.dld.2010.02.008.
Shannon Glaser 1 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
Affiliations

Affiliation

  • 1 Scott & White Digestive Disease Research Center, Scott & White, Temple, TX 76504, United States. sglaser@tamu.edu
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.

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