Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice.

Abstract

Sox4 participates in the progression of embryo development and regulation of apoptosis in tumors. However, the effect and mechanism of Sox4 in myocardial infarction (MI) remainsunclear. Therefore, we aimedatexaminingthe role and molecular mechanism of Sox4 in the process of cardiomyocytes apoptosis during MI. The expression of Sox4 were obviously increased both in MI mice and in neonatal mouse cardiomyocytes treated with H2 O2 . Overexpression of Sox4 promoted cardiomyocyteapoptosis with or without H2 O2 , whereas knocking down of Sox4 alleviated H2 O2 -induced apoptosis in cardiomyocytes. Furthermore, silencing Sox4 by AAV-9 carried short hairpin RNA targeting Sox4 (AAV-9-sh-Sox4) markedly decreased cardiac infarct area, imprfoved cardiac dysfunction, and reversed apoptosis in MI mice. Mechanistically, there is a potential Sox4-binding site in the promoter region of Bim, and forced expression of Sox4 significantly promoted Bim expression in cultured cardiomyocytes with or without H2 O2 , whereas knocking down of Sox4 inhibited the expression of Bim. Further studies showed that silencing Bim attenuated Sox4-induced apoptosis in cardiomyocytes, indicating that Sox4 promoted cardiomyocytes apoptosis through regulation of Bim expression, which can be used as a potential therapeutic target for MI.