Work

(Pro)renin receptor promotes cardiomyocyte senescence via tripartite motif-containing 24-mediated stabilization of p53 in diabetic cardiomyopathy

Year: 2025

Type: article

Abstract: Diabetic cardiomyopathy (DCM) is a major complication of diabetes and a leading contributor to heart failure, in which cardiomyocyte senescence plays an increasingly recognized role. However, the underlying mechanisms driving this process remain poorly defined. Here, we identify the (pro)renin receptor (PRR) as a critical mediator of cardiomyocyte senescence in DCM. Using a high-fat diet and streptozotocin (STZ)-induced DCM mouse model, as well as primary cardiomyocytes exposed to high glucose and palmitic acid, we demonstrate that PRR expression is significantly upregulated in diabetic hearts and closely associated with key senescence markers, including SA-β-gal, γ-H2AX, p16, and p21. PRR overexpression exacerbates these senescence phenotypes and promotes the secretion of profibrotic senescence-associated secretory phenotype factors, contributing to increased myocardial fibrosis and cardiac dysfunction. Mechanistically, PRR stabilizes the p53 protein by inhibiting tripartite motif-containing 24 (TRIM24)-mediated ubiquitination and proteasomal degradation, thereby activating the p53-p21 axis. These findings reveal a novel role of the PRR in diabetic myocardial senescence and provide potential therapeutic targets for attenuating DCM progression.

Source: Acta Biochimica et Biophysica Sinica

DOI: 10.3724/abbs.2025185