TRIM52 Protects Against Doxorubicin-Induced Cardiac Inflammation, Oxidative Stress and Cardiac Injury

Tripartite motif 52 (TRIM52) has been identified as a key regulator of inflammatory responses. However, its involvement in doxorubicin (DOX)-induced cardiotoxicity (DIC) and the underlying molecular mechanisms remain poorly understood. To investigate the functional role of TRIM52, we employed an adeno-associated virus serotype 9 (AAV9) delivery system to achieve cardiac-specific Trim52 knockout via tail-vein injection. C57BL/6 mice received intraperitoneal DOX (5 mg/kg, administered once a week, with a total cumulative dose of 15 mg/kg). Myocardial injury was evaluated by histopathological assessment and molecular profiling of cardiac tissues, complemented by in vitro mechanistic studies using neonatal mouse cardiomyocytes. In vivo and in vitro studies revealed that DOX treatment significantly upregulated TRIM52 expression. Trim52 deficiency effectively mitigated DOX-induced cardiac injury and dysfunction, concomitantly attenuating oxidative stress and inflammatory responses. Mechanistically, Trim52 deletion markedly enhanced PI3K and AKT phosphorylation, indicating that PI3K/AKT pathway activation underlies the cardioprotective effects of TRIM52 deficiency. Our findings demonstrate that TRIM52 deletion activates PI3K/AKT signalling and attenuates DOX-induced oxidative and inflammatory myocardial damage. These data identify TRIM52 as a potential therapeutic target for mitigating DIC.