DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing MitophagySummary

Min Xu; Hualian Hang; Miao Huang; Jichang Li; Dongwei Xu; Junzhe Jiao; Fang Wang; Hailong Wu; Xuehua Sun; Jinyang Gu; Xiaoni Kong; Yueqiu Gao

Cellular and Molecular Gastroenterology and Hepatology (Jan 2021)

DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing MitophagySummary

Min Xu,
Hualian Hang,
Miao Huang,
Jichang Li,
Dongwei Xu,
Junzhe Jiao,
Fang Wang,
Hailong Wu,
Xuehua Sun,
Jinyang Gu,
Xiaoni Kong,
Yueqiu Gao

Affiliations

Min Xu: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China
Hualian Hang: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Miao Huang: Department of Transplantation, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Jichang Li: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China
Dongwei Xu: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Junzhe Jiao: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China
Fang Wang: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China
Hailong Wu: Shanghai Key Laboratory for Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine & Health Science, Shanghai, China
Xuehua Sun: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China
Jinyang Gu: Department of Transplantation, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Jinyang Gu, MD, PhD.
Xiaoni Kong: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China; Correspondence Address correspondence to: Xiaoni Kong, PhD, Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, 528 Zhangheng Road, Shanghai, China 201203.
Yueqiu Gao: Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shangha, China; Yueqiu Gao, MD.

Journal volume & issue: Vol. 12, no. 2
pp. 567 – 584

Abstract

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Background & Aims: DJ-1 is universally expressed in various tissues and organs and is involved in the physiological processes in various liver diseases. However, the role of DJ-1 in liver ischemia-reperfusion (I/R) injury is largely unknown. Methods: In this study, we first examined the DJ-1 expression changes in the liver tissues of mice and clinical donor after hepatic I/R by both quantitative polymerase chain reaction and Western blotting assays. Then we investigated the role of DJ-1 in I/R injury by using a murine liver I/R model. Results: We demonstrated that DJ-1 down-regulation in both human and mouse liver tissues in response to I/R injury and Dj-1 deficiency in hepatocytes but not in myeloid cells could significantly ameliorate I/R induced liver injury and inflammatory responses. This hepatoprotective effect was dependent on enhanced autophagy in Dj-1 knockout mice, because inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect on hepatic I/R injury in Dj-1 knockout mice. Conclusions: Dj-1 deficiency in hepatocytes significantly enhanced mitochondrial accumulation and protein stability of PARKIN, which in turn promotes the onset of mitophagy resulting in elevated clearance of damaged mitochondria during I/R injury.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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