Taurocholic acid prevents biliary damage induced by hepatic artery ligation in cholestatic rats
| Autor: | Romina Mancinelli, Shannon Glaser, Heather Francis, Guido Carpino, Gianfranco Alpini, Luigi Pannarale, Shelley Kopriva, Julie Venter, Paolo Onori, Roberta Sferra, Eugenio Gaudio, Antonella Vetuschi, Antonio Franchitto, Mellanie White, Yoshiyuki Ueno |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Taurocholic Acid Vascular Endothelial Growth Factor A Cholagogues and Choleretics medicine.medical_specialty CCL4 digestive system Article Primary sclerosing cholangitis chemistry.chemical_compound Hepatic Artery Cholestasis Internal medicine medicine Animals mitosis camp intrahepatic biliary epithelium vegf apoptosis Ligation Cells Cultured Cell Proliferation Hepatology Bile duct business.industry Gastroenterology Kinase insert domain receptor medicine.disease Taurocholic acid Immunohistochemistry Vascular Endothelial Growth Factor Receptor-2 Rats Inbred F344 digestive system diseases Rats Vascular endothelial growth factor Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Bile Ducts business |
| Zdroj: | Digestive and Liver Disease. 42:709-717 |
| ISSN: | 1590-8658 |
| DOI: | 10.1016/j.dld.2010.02.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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