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

被引：26
作者：
Xu, Min [1 ]
Hang, Hualian [2 ]
Huang, Miao [3 ]
Li, Jichang [1 ]
Xu, Dongwei [2 ]
Jiao, Junzhe [1 ]
Wang, Fang [1 ]
Wu, Haiiong [4 ]
Sun, Xuehua [1 ]
Gu, Jinyang [3 ]
Kong, Xiaoni [1 ]
Gao, Yueqiu [1 ]
机构：
[1] Shanghai Univ Chinese Tradit Med, Dept Liver Dis, Cent Lab, ShuGuang Hosp, 528 Zhangheng Rd, Shanghai 201203, Peoples R China
[2] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Liver Surg, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Transplantat, Shanghai, Peoples R China
[4] Shanghai Univ Med & Hlth Sci, Collaborat Res Ctr, Shanghai Key Lab Mol Imaging, Shanghai, Peoples R China
来源：
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2021年 / 12卷 / 02期
基金：
中国国家自然科学基金;
关键词：
DJ-1; Liver I/R Injury; PARKIN; Mitophagy; MITOCHONDRIAL-FUNCTION; AUTOPHAGY; ISCHEMIA/REPERFUSION; PARKIN; PROTECTS; PATHWAY; PINK1; GENE; CARDIOPROTECTION; OVEREXPRESSION;
D O I：
10.1016/j.jcmgh.2021.03.007
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
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.
引用
收藏
页码：567 / 584
页数：18
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