Hepatocyte-Specific HuR Protects Against Acetaminophen-Induced Liver Injury in Mice.

J Cell Mol Med

Institute of Medical Sciences, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Published: November 2024

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury (DILI) in many countries. Hepatocyte proliferation, autophagy and antioxidant capacity are crucial to the prognosis of APAP-induced liver injury, but the underlying mechanisms are not fully understood. Here, we found that human antigen R (HuR) protein expression was markedly increased in the model of APAP-induced liver injury, and conditional hepatocyte-specific HuR knockout aggravated APAP-induced liver injury in mice. Further investigation of the underlying mechanisms of HuR's protective effects showed that conditional hepatocyte-specific HuR knockout reduced the protein expression of cyclin A1, cyclin B1, cyclin D1, CDK2, ATG3, ATG5, ATG7 and NRF2 in mice, reducing hepatocyte proliferation, autophagy and antioxidant capacity. Mechanistically, HuR could physically associate with the 3'-untranslated regions (UTRs) of cyclin A1, cyclin B1, cyclin D1, Cdk2, Atg3, Atg5, Atg7 and Nrf2 mRNAs, thereby regulating their translation. These findings suggest that HuR attenuates APAP-induced liver injury by regulating hepatocyte proliferation, autophagy and antioxidant capacity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606931PMC
http://dx.doi.org/10.1111/jcmm.70246DOI Listing

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