title: Hypoxia-inducible factor-2α promotes hepatocyte apoptosis during cholestasis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These findings implied the contribution of HIF-2α to cholestasis-mediated hepatocyte apoptosis.
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Tianfei
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Miao
authors.affiliation: Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Zhaolian
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai Children's Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Digestive Disease Laboratory and Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Liver Surgery and Liver Transplantation Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
keywords: apoptosis; biliary atresia; cholestasis; hepatocyte; hypoxia-inducible factor-2α