Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

Eunyoung Tak; Dong Hwan Jung; Seok Hwan Kim; Gil Chun Park; Dae Young Jun; Jooyoung Lee; Bo hyun Jung; Varvara A. Kirchner; Shin Hwang; Gi Won Song; Sung Gyu Lee

doi:10.1016/j.taap.2016.11.016

Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

Eunyoung Tak, Dong Hwan Jung, Seok Hwan Kim, Gil Chun Park, Dae Young Jun, Jooyoung Lee, Bo hyun Jung, Varvara A. Kirchner, Shin Hwang, Gi Won Song, Sung Gyu Lee

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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.

Original language	English (US)
Pages (from-to)	72-81
Number of pages	10
Journal	Toxicology and Applied Pharmacology
Volume	314
DOIs	https://doi.org/10.1016/j.taap.2016.11.016
State	Published - Jan 1 2017

Bibliographical note

Funding Information:
The present research work was partially supported by research funds from the Asan Institute for Life Sciences (Tak EY, 15-662 ), the National Research Foundation of Korea ( NRF-2015K1A4A3046807 ), Mitsubishi Tanabe Pharma Korea Co., Ltd. (Lee SG, 2015-1390 ) and Yuhan corporation (Lee SG, 2015-0908 ).

Publisher Copyright:
© 2016 The Authors

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

Acute liver failure
CD39
CD73
HIF-1α

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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.",

keywords = "Acute liver failure, CD39, CD73, HIF-1α",

author = "Eunyoung Tak and Jung, {Dong Hwan} and Kim, {Seok Hwan} and Park, {Gil Chun} and Jun, {Dae Young} and Jooyoung Lee and Jung, {Bo hyun} and Kirchner, {Varvara A.} and Shin Hwang and Song, {Gi Won} and Lee, {Sung Gyu}",

note = "Funding Information: The present research work was partially supported by research funds from the Asan Institute for Life Sciences (Tak EY, 15-662 ), the National Research Foundation of Korea ( NRF-2015K1A4A3046807 ), Mitsubishi Tanabe Pharma Korea Co., Ltd. (Lee SG, 2015-1390 ) and Yuhan corporation (Lee SG, 2015-0908 ). Publisher Copyright: {\textcopyright} 2016 The Authors Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.taap.2016.11.016",

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AU - Tak, Eunyoung

AU - Jung, Dong Hwan

AU - Kim, Seok Hwan

AU - Park, Gil Chun

AU - Jun, Dae Young

AU - Lee, Jooyoung

AU - Jung, Bo hyun

AU - Kirchner, Varvara A.

AU - Hwang, Shin

AU - Song, Gi Won

AU - Lee, Sung Gyu

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PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

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Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

Abstract

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Keywords

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