Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells

Biochemical and Biophysical Research Communications
Kang Mo KimHyo-Suk Lee

Abstract

In cholestatic liver diseases, bile acids induce hepatocyte apoptosis and thus cause liver injury, but hepatic stellate cells (HSCs) survive in the presence of bile acids. We attempted to analyze anti-apoptotic signaling pathways in HSCs against bile acid-induced apoptosis. In immortalized human HSCs and primarily cultured rat HSCs, bile acid treatment increased the expression levels of cyclooxygenase-2 (COX-2) and Mcl-1. COX-2 induction was found to be due to transcriptional enhancement dependent on p42/44, p38 MAPK, and JNK activation, whereas Mcl-1 induction resulted from bile acid-mediated protein stabilization in a Raf-1-dependent manner. Moreover, the inhibitions of either COX-2 activity by celecoxib or Mcl-1 induction by siRNA transfection rendered HSCs susceptible to bile acid-induced apoptosis. These results imply that the bile acid-mediated inductions of COX-2 and Mcl-1 may lead to HSC survival in cholestatic liver diseases.

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Citations

Aug 2, 2008·Nature Reviews. Drug Discovery·Charles ThomasKristina Schoonjans
Dec 17, 2008·World Journal of Gastroenterology : WJG·Alphonse-E Sirica
Apr 19, 2011·Annual Review of Biochemistry·Joshua Wollam, Adam Antebi
Jan 6, 2016·International Journal of Molecular Sciences·Karin Komposch, Maria Sibilia
Jan 29, 2009·Gastroenterología y hepatología·Juan ClàriaNatàlia Ferré

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