title: Deficiency of DJ-1 Ameliorates Liver Fibrosis through Inhibition of Hepatic ROS Production and Inflammation.
abstract: 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.
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of liver diseases, Shuguang Hospital affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of liver diseases, Shuguang Hospital affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Kong
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071617:Protein Deglycase DJ-1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D002251:Carbon Tetrachloride; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: DJ-1; ROS; inflammation; lipid peroxidation.; liver fibrosis; liver injury