The Function And Mechanism Study Of DJ-1 In CCl4-induced Mouse Liver Fibrosis Model

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)is also called DJ-1(protein deglycase 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)mice 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 inflammation and hepatocyte proliferation compared to WT mice.In vitro hepatic stellate cells(HSC)activation assays indicated that DJ-1 has no direct effect on the activation of HSC in the context of with or without TGF? 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 HSC.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.