ZC3H13-induced KLRB1 upregulation relieves the injury of myocardial infarction through N [6]-methyladenosine methylation

Myocardial infarction (MI) is caused by blocked blood flow that leads to tissue damage and impaired cardiac function. This study explored the function and mechanism of Killer Cell Lectin-Like Receptor B1 (KLRB1) in MI, and examined how n6-methyladenosine (m6A) modification regulates its function. The expressions of KLRB1 in MI cell model was evaluated using qRT-PCR and western blotting. The effect of KLRB1 on MI injury was assessed in both cell and animal models. In cell model, cell viability, apoptosis, and inflammation were evaluated using CCK-8, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In animal model, cardiac function, infract area, structure, apoptosis, injury marker, and inflammation were examined through echocardiography, 2,3,5-Triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and ELISA. The relationship between KLRB1 and ZC3H13 was explored using qRT-PCR, western blotting, and methylated RNA immunoprecipitation (MeRIP) assay. KLRB1 showed substantial downregulation in MI. KLRB1 was downregulated in MI, and its overexpression enhanced cell viability, reduced apoptosis and inflammation, and improved infarct size and tissue structure in vivo. ZC3H13 was downregulated in MI. ZC3H13 was downregulated in the MI, and its overexpression increased KLRB1 mRNA and protein levels via regulating KLRB1 m6A modification. In conclusion, these findings suggest that KLRB1 alleviates the MI injury, and ZC3H13 induces the upregulation of KLRB1 through m6A modification. These results may provide insight into the ZC3H13/KLRB1 axis as a potential therapeutic avenue for reducing myocardial injury and improving cardiac outcomes after MI.