Hypoxia-inducible factor-2α promotes hepatocyte apoptosis during cholestasis.

Abstract

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.

• Authors: Xiangwei Hua, Tianfei Lu, Jiang Zhang, Qi Miao, Zhaolian Bian, Haiyan Zhang, Shanshan Huang, Weiwei Lin, Zhifeng Xi, Ming Zhang, Qimin Chen, Xiong Ma, Jianjun Zhang, Qiang Xia
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 47 Issue 1 Pg. 95-102 (Jan 2017) ISSN: 1386-6346 [Print] Netherlands
• PMID: 26992434 (Publication Type: Journal Article)
• Copyright: © 2016 The Japan Society of Hepatology.