摘要
Reactive oxygen species(ROS)and immune response play critical roles in the progression of liver diseases.DJ-1,also known as Parkinson disease 7(Park7),is extensively expressed in cells and tissues,where it governs numerous biological functions including chaperone activity,protease function,transcriptional and mitochondrial regulation,and ROS modulation.Moreover,we have established that DJ-1 plays a critical role in initiating an inflammatory response by modulating ROS generation.Therefore,DJ-1 may play an important role in the progression of liver diseases by modulating ROS and the immune response.Recently,we have shown that DJ-1 deficiency negatively regulates proliferation of hepatic progenitor cells(HPCs)by impairing the formation of HPC-associated fibrosis and inflammatory niches.Deficiency of DJ-1 ameliorates liver fibrosis by inhibiting hepatic ROS production and inflammation;moreover,in a classic diethylnitrosamine(DEN)-mediated hepatocellular carcinoma(HCC)mouse model,deletion of DJ-1 ameliorates tumorigenesis and HCC cell proliferation by regulating hepatic inflammation and reducing the activity of the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3)signaling pathway.Taken together,these data suggest a critical function for,and therapeutic value of,DJ-1 in treatment of liver diseases.The aim of this review is to summarize these functions and the underlying molecular mechanisms of DJ-1 in liver diseases,and to highlight the potential therapeutic value and future research direction of DJ-1 in liver diseases.
基金
This work was supported by the National Natural Science Foundation of China 81670562 and 31300742 to X.Kong.
