Deficiency of DJ-1 Ameliorates Liver Fibrosis through Inhibition of Hepatic ROS Production and Inflammation.
Deficiency of DJ-1 Ameliorates Liver Fibrosis through Inhibition of Hepatic ROS Production and Inflammation.
复制标题
DJ-1 缺乏可通过抑制肝脏 ROS 产生和炎症来改善肝纤维化
DOI：
10.7150/ijbs.15154
复制
发表时间：
2016
影响因子：
9.2
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Yu Y;Sun X;Gu J;Yu C;Wen Y;Gao Y;Xia Q;Kong X
肝纤维化是一个全球性的健康问题，以往的研究表明，活性氧自由基(ROS)在肝纤维化形成中起着重要作用。帕金森病(常染色体隐性遗传，早发性)7(Park7)，也称为DJ-1，在调节细胞内ROS水平方面起着至关重要的作用。因此，DJ-1可能在肝纤维化形成中发挥作用，DJ-1的调控可能是一种有前途的治疗方法。用四氯化碳(CCl4)诱导野生型(WT)和DJ-1基因敲除(DJ-1 KO)小鼠肝纤维化或急性肝损伤。结果表明，DJ-1的耗竭显著钝化了肝纤维化，并伴随着肝损伤和ROS产生的显著减少。在急性CCl_4模型中，与WT小鼠相比，DJ-1缺乏具有肝脏保护作用，表现为肝脏损伤减轻，ROS水平降低，肝脏炎症和肝细胞增殖减轻。体外肝星状细胞(HSCs)活化实验表明，在有或无转化生长因子β处理的情况下，DJ-1对HSC的激活没有直接影响。因此，我们目前的研究表明，在CCl4诱导的肝纤维化中，DJ-1缺乏通过抑制ROS的产生和肝损伤，进而间接影响HSCs的激活来减轻小鼠的纤维化。这些结果与前人关于ROS促进HSC活化和纤维化发展的研究一致，提示DJ-1在治疗肝纤维化方面有一定的治疗价值。
Liver fibrosis is a global health problem and previous studies have demonstrated that reactive oxygen species (ROS) play important roles in fibrogenesis. Parkinson disease (autosomal recessive, early onset) 7 (Park7) also called DJ-1 has an essential role in modulating cellular ROS levels. DJ-1 therefore may play functions in liver fibrogenesis and modulation of DJ-1 may be a promising therapeutic approach. Here, wild-type (WT) and DJ-1 knockout (DJ-1 KO) mice were administrated with carbon tetrachloride (CCl4) to induce liver fibrosis or acute liver injury. Results showed that DJ-1 depletion significantly blunted liver fibrosis, accompanied by marked reductions in liver injury and ROS production. In the acute CCl4 model, deficiency of DJ-1 showed hepatic protective functions as evidenced by decreased hepatic damage, reduced ROS levels, diminished hepatic inflammation and hepatocyte proliferation compared to WT mice. In vitro hepatic stellate cells (HSCs) activation assays indicated that DJ-1 has no direct effect on the activation of HSCs in the context of with or without TGFβ treatment. Thus our present study demonstrates that in CCl4-induced liver fibrosis, DJ-1 deficiency attenuates mice fibrosis by inhibiting ROS production and liver injury, and further indirectly affecting the activation of HSCs. These results are in line with previous studies that ROS promote HSC activation and fibrosis development, and suggest the therapeutic value of DJ-1 in treatment of liver fibrosis.
登录
查看更多内容
影响因子：
7.4
作者：
Reuter, Simone;Gupta, Subash C.;Chaturvedi, Madan M.;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
影响因子：
13.5
作者：
Nieto, N;Friedman, SL;Cederbaum, AI
通讯作者：
Cederbaum, AI
影响因子：
7.7
作者：
Taira, T;Saito, Y;Ariga, H
通讯作者：
Ariga, H
DOI：
10.1084/jem.20102049
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bulua AC;Simon A;Maddipati R;Pelletier M;Park H;Kim KY;Sack MN;Kastner DL;Siegel RM
通讯作者：
Siegel RM
影响因子：
44.1
作者：
Liu, Wenjun;Wu, Hailong;Gao, Wei-Qiang
通讯作者：
Gao, Wei-Qiang