title: Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure.
abstract: Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF. To test our hypothesis, liver biopsies were obtained and we found that CD39 and CD73 mRNA and proteins from human specimens were dramatically elevated in ALF. We investigated that induction of CD39 and CD73 in ALF-related with wild type mice. In contrast, deletion of cd39 and cd73 mice has severe ALF. In this study, we concluded that CD39 and CD73 are molecular targets for the development of drugs for ALF patients care.
authors.affiliation: Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Tak
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Jung
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seok-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Gil-Chun
authors.initials: GC
authors.lastname: Park
authors.affiliation: Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jun
authors.affiliation: Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Jung
authors.affiliation: Division of Transplantation, Department of Surgery and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Varvara A
authors.initials: VA
authors.lastname: Kirchner
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: drsong71@amc.seoul.kr.
authors.forename: Gi-Won
authors.initials: GW
authors.lastname: Song
authors.affiliation: Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Gyu
authors.initials: SG
authors.lastname: Lee
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001081:Apyrase / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D017114:Liver Failure, Acute / Q000503:physiopathology*; D008297:Male; D051379:Mice; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen
keywords: Acute liver failure; CD39; CD73; HIF-1α