S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells
- Kim, Kang Mo; Yoon, Jung-Hwan; Gwak, Geum-Youn; Kim, Won; Lee, Sung Hee; Jang, Ja June; Lee, Hyo-Suk
- Issue Date
- Academic Press
- Biochem. Biophys. Res. Commun. 342 (2006) 1108-1113.
- Animals; Apoptosis/drug effects/*physiology; Cell Line; Cell Survival/drug effects; Chenodeoxycholic Acid/administration & dosage/*metabolism; Cyclooxygenase 2/*metabolism; Dose-Response Relationship, Drug; Hepatocytes/drug effects/*metabolism; Humans; Neoplasm Proteins/*metabolism; Proto-Oncogene Proteins c-bcl-2/*metabolism; Rats; Signal Transduction/drug effects/physiology
- 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.
- Files in This Item: There are no files associated with this item.