DNA methyltransferase 1-mediated methylation of midkine regulate myocardial ischemia-reperfusion injury via the Notch2/Hes1 axis

myocardial ischemia-reperfusion injury (MI/RI) threatens people's lives. Midkine (MDK) has a protective effect against MI/RI. DNA methyltransferase 1 (DNMT1) is closely associated with MI/RI. Mouse cardiomyocytes were isolated to establish a model of myocardial ischemia-reperfusion. Subsequently, the viability, apoptosis, and inflammatory factors of the cardiomyocytes treated under different conditions were measured. Western blotting was employed to examine the expression of related proteins. Chromatin immunoprecipitation (CHIP) and dual-luciferase reporter gene assays were conducted to verify the relationships among the DNMT1, MDK, and Notch2/Hes1 signaling pathways. The expression of MDK was reduced in the MI/RI cell model, while Notch2/Hes1 was activated. Overexpression of MDK mitigated the injury associated with MI/RI. Methylation modification of DNMT1 downregulated MDK, thereby mediating the Notch2/Hes1 pathway. The methylation modification of DNMT1 on MDK regulated the progression of MI/RI. The methylation modification of MDK by DNMT1 likely downregulates the Notch2/Hes1 pathway, thereby influencing MI/RI.