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Hypoxia‐inducible factor‐2α promotes hepatocyte apoptosis during cholestasis
Author(s) -
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
Publication year - 2017
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12708
Subject(s) - cholestasis , apoptosis , hepatocyte , western blot , tunel assay , biology , hepatocyte growth factor , stromal cell , immunohistochemistry , terminal deoxynucleotidyl transferase , hypoxia inducible factors , hypoxia (environmental) , microbiology and biotechnology , cancer research , pathology , endocrinology , chemistry , immunology , in vitro , medicine , biochemistry , receptor , organic chemistry , oxygen , gene
Aim Hypoxia‐inducible factor‐2α (HIF‐2α) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF‐2α in cholestasis‐mediated hepatocyte apoptosis.Methods Hypoxia‐inducible factor‐2α 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.Results In pediatric and murine cholestatic liver tissues, HIF‐2α protein was widely expressed in the nucleus of parenchymal cells as well as in stromal cells. Hepatocyte HIF‐2α 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‐2α deletion could alleviate cholestasis‐mediated hepatocyte apoptosis and regulate the expression of c‐myc, p53, and Bax proteins.Conclusion These findings implied the contribution of HIF‐2α to cholestasis‐mediated hepatocyte apoptosis.