Research Paper Volume 13, Issue 14 pp 18879—18893
Myeloid DJ-1 deficiency protects acetaminophen-induced acute liver injury through decreasing inflammatory response
- 1 Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2 Central Laboratory, Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China
- 3 Department of General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Received: March 25, 2021 Accepted: July 9, 2021 Published: July 21, 2021https://doi.org/10.18632/aging.203340
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: DJ-1 (also known as PARK7), a noted protein implicated in modulating ROS production and immune response, has been observed to play critical roles in the pathogenesis of many forms of liver disease through multiple mechanisms. However, its role and specific mechanism in acetaminophen (APAP) -induced liver injury have not been explored.
Results: In this present study, by employing an acute liver injury induced by APAP overdose mouse model, we demonstrated that DJ-1 knockout (DJ-1−/−) mice showed reduced liver injury and lower mortality. In accordance with these changes, there were also alleviating inflammatory responses in both the serum and the liver of the DJ-1−/− mice compared to those of the wild-type (WT) mice. Functional experiments showed that APAP metabolism did not affected by DJ-1 deficiency. In addition, to investigate DJ-1 modulates which kind of cell types during APAP-overdose-induced acute liver injury, hepatocyte-specific DJ-1-knockout (Alb-DJ-1−/−) and myeloid-specific DJ-1-knockout (Lysm-DJ-1−/−) mice were generated. Interestingly, hepatic deletion of DJ-1 did not protect APAP-overdose induced hepatotoxicity and inflammation, whereas Lysm-DJ-1−/− mice showed similar protective effects as DJ-1−/− mice which suggest that the protective effects of deletion of DJ-1 was through modulating myeloid cell function. Consistently, there were alleviated pro-inflammatory cells infiltration and reduced reactive oxygen species (ROS) production in the liver of Lysm-DJ-1−/− mice relative to control mice.
Conclusion: our findings clearly defined that deletion of DJ-1 protects APAP-induced acute liver injury through decreasing inflammatory response, and suggest DJ-1 as a potential therapeutic and/or prophylactic target of APAP-induced acute liver injury.
APAP: Acetaminophen; ROS: reactive oxygen species; ALF: acute liver failure; ER: endoplasmic reticulum; IL-1: interleukin-1; TNF-α: tumor necrosis factor-α; Park7: Parkinson disease protein 7; HPC: hepatic progenitor cell; HCC: hepatocellular carcinoma cell; WT: wild-type; ALT: alanine aminotransferase; AST: aspartate aminotransferase; IACUC: Institutional Animal Care and Use Committees; IHC: immunohistochemistry.