DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing Mitophagy.
DJ-1 Deficiency in Hepatocytes Improves Liver Ischemia-Reperfusion Injury by Enhancing Mitophagy.
复制标题
肝细胞中 DJ-1 缺乏通过增强线粒体自噬改善肝脏缺血再灌注损伤
DOI：
10.1016/j.jcmgh.2021.03.007
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发表时间：
2021
影响因子：
7.2
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Xu M;Hang H;Huang M;Li J;Xu D;Jiao J;Wang F;Wu H;Sun X;Gu J;Kong X;Gao Y
DJ-1广泛表达于多种组织器官，参与多种肝病的生理过程。然而，DJ-1在肝脏缺血再灌注(I/R)损伤中的作用尚不清楚。在本研究中，我们首先通过定量聚合酶链式反应和Western blotting检测了DJ-1在小鼠和临床供体肝脏I/R后的表达变化。然后利用小鼠肝脏I/R模型，研究DJ-1在肝脏I/R损伤中的作用。我们证明，在人和小鼠肝组织中，DJ-1在I/R损伤和DJ-1缺乏性肝细胞中的表达下调，但在髓细胞中的表达不下调，可以显着改善I/R所致的肝损伤和炎症反应。DJ-1基因敲除小鼠的这种保护肝脏的作用依赖于增强的自噬，因为3-甲基腺嘌呤和氯喹抑制自噬可以逆转DJ-1基因敲除小鼠对肝脏I/R损伤的保护作用。肝细胞DJ-1缺乏显著增加了Parkin的线粒体积聚和蛋白稳定性，进而促进了线粒体吞噬的开始，导致I/R损伤时受损线粒体的清除增加。
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. 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. 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. 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.
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影响因子：
--
作者：
Cursio R;Colosetti P;Gugenheim J
通讯作者：
Gugenheim J
影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
影响因子：
5.1
作者：
Luan, Shaorong;Yun, Xinming;Huang, Qingchun
通讯作者：
Huang, Qingchun
影响因子：
9.8
作者：
Aron L;Klein P;Pham TT;Kramer ER;Wurst W;Klein R
通讯作者：
Klein R