Growth Factor Receptor-Binding Protein 10 Promotes High Glucose-Induced H9c2 Cardiomyoblast Apoptosis via Inhibition of the ERK1/2 and JAK2/STAT3 Signaling Pathways

Abstract

Cardiomyocyte apoptosis is crucial in the occurrence of diabetic cardiomyopathy; thus, it is important to elucidate the underlying mechanisms involved in elevated glucose and cardiomyocyte apoptosis. Growth factor receptor-binding protein 10 (Grb10) has been proved to participate in the regulation of cell proliferation, migration, and apoptosis. The purpose of this study was to explore the role of Grb10 in high glucose-induced H9c2 cardiomyoblast apoptosis and investigate the underlying molecular mechanisms. H9c2 cardiomyoblasts were cultured and exposed to an elevated glucose at a level of 33 mM. Grb10 expression was inhibited using small interfering RNA (siRNA), and the activities of ERK1/2 and STAT3 were stimulated by specific activators. Western blot analysis was used to detect the expression levels of Grb10, (phosphorylated) ERK1/2, (phosphorylated) JAK2/STAT3, Bax, Bcl2, and cleaved caspase-3, and the TdT-mediated UTP nick end labeling test was used to measure the apoptosis rate. High glucose treatment in H9c2 cardiomyoblasts led to increased Grb10 expression and cell apoptosis. Grb10-siRNA treatment attenuated high glucose-induced H9c2 cell apoptosis. Furthermore, the repressed activities of ERK1/2 and JAK2/STAT3 signaling pathways induced by high glucose were reversed by Grb10-siRNA treatment. Upregulated ERK1/2 or STAT3 activity partially reversed the apoptosis of H9c2 cardiomyoblast caused by high glucose treatment. Our findings show that Grb10 is involved in high glucose-induced H9c2 cardiomyoblast apoptosis and might exert its apoptosis-promoting role through inhibition of the ERK1/2 and JAK2/STAT3 signaling pathways.