Hypoxia-inducible factor-2 promotes hepatocyte apoptosis during cholestasis

作者：Hua, Xiangwei; Lu, Tianfei; Zhang, Jiang; Miao, Qi; Bian, Zhaolian; Zhang, Haiyan; Huang, Shanshan; Lin, Weiwei; Xi, Zhifeng; Zhang, Ming; Chen, Qimin; Ma, Xiong; Zhang, Jianjun; Xia, Qiang^*

来源：Hepatology Research, 2017, 47(1): 95-102.

DOI：10.1111/hepr.12708

• apoptosis
• biliary atresia
• cholestasis
• hepatocyte
• hypoxia-inducible factor-2

AimHypoxia-inducible factor-2 (HIF-2) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF-2 in cholestasis-mediated hepatocyte apoptosis. @@@ MethodsHypoxia-inducible factor-2 expression was measured by immunohistochemistry and confocal microscopy. Hepatic apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. The cholestatic mouse model was treated with bile duct ligation. The c-myc, p53, and Bax protein levels were measured with Western blot analysis. @@@ ResultsIn pediatric and murine cholestatic liver tissues, HIF-2 protein was widely expressed in the nucleus of parenchymal cells as well as in stromal cells. Hepatocyte HIF-2 expression was significantly elevated at the early stage of pediatric cholestasis and decreased at the late stage. In both in vivo and in vitro murine studies, HIF-2 deletion could alleviate cholestasis-mediated hepatocyte apoptosis and regulate the expression of c-myc, p53, and Bax proteins. @@@ ConclusionThese findings implied the contribution of HIF-2 to cholestasis-mediated hepatocyte apoptosis.

• 出版日期2017-1
• 单位上海交通大学