Myofibroblast specific knockdown of NSUN2 suppresses cardiac fibrosis post-myocardial infarction.

Abstract

Cardiac fibrosis, a common pathological process characterized by excessive deposition of extracellular matrix components in the myocardium, poses a critical challenge in the field of cardiovascular research and clinical practice. 5-Methylcytosine (m5C) is an extensive post-transcriptional RNA modification known to participate in various cellular responses and biological processes by regulating RNA metabolism. However, it remains unclear whether m5C RNA modifications exert regulatory effects on cardiovascular diseases, particularly cardiac fibrosis. Here, we report that NSUN2, a typical m5C methyltransferase, affects the RNA stability of HuR through m5C modification, promoting the development of cardiac fibrosis. Upon the conditional knockdown of NSUN2 specifically in myofibroblasts, the extent of cardiac fibrosis was suppressed. In conclusion, we specifically knocked down NSUN2 in cardiac myofibroblasts, which further reduced the RNA stability of HuR and thus ameliorated cardiac fibrosis caused by myocardial ischemia, offering a new therapeutic target for the clinical treatment of cardiac fibrosis.