Protective effects of regulating Egr-1 or TOE1 in CVB3-infected viral myocarditis

The etiology and disease processes of viral myocarditis remain elusive. However, it is unknown whether early growth response-1 (Egr-1) and Target Egr-1 (TOE1) play a role in viral myocarditis. CVB3 infection was used to induce a mouse model of myocarditis, and cultured neonatal mouse cardiomyocytes were exposed to CVB3 to establish a cell model of VMC. RT-qPCR was used to determine mRNA expression levels of Egr-1, TOE1, P53, P21, and CVB3. Western blot analysis was employed to determine protein expression levels of Egr-1, TOE1, BAX, and BCL-2, and HE staining was utilized to observe pathological changes of myocardial inflammation. TUNEL staining was used to detect apoptosis levels in cardiomyocytes. In vivo results revealed that mRNA and protein expression levels of Egr-1 and TOE1 in myocardial tissues increased with prolonged CVB3 infection, BAX expression levels were upregulated, and BCL-2 expression levels were down-regulated. Moreover, in vitro findings demonstrated that 100nM Egr-1 siRNA and 100nM TOE1 siRNA could separately inhibit Egr-1 and TOE1 mRNA expression. The down-regulation of Egr-1 or TOE1 down-regulated P53, P21, and CVB3 mRNA expression in CVB3-infected myocardial cells decreased apoptotic protein BAX expression and increased anti-apoptotic protein BCL-2 expression. TUNEL assay revealed that Egr-1 or TOE1 gene down-regulation reduced CVB3 infection-induced apoptosis in cardiac myocytes. This study demonstrated that down-regulation of Egr-1 and TOE1 genes could inhibit cardiomyocyte apoptosis triggered by CVB3 virus infection and reduce CVB3 virus amplification, thus exerting a protective effect on myocardium.