Osteoprotegerin prompts cardiomyocyte hypertrophy via FAK/BECLIN1 mediated autophagy inhibition

Abstract

Aim It has been reported that Osteoprotegerin (OPG) induces cardiomyocyte hypertrophy, but the mechanism remains unclear. This study was to investigate the role of Focal Adhesion Kinase (FAK) pathway in the OPG induced hypertrophy in cultured cardiomyocytes.Methods The H9C2 line of rat cardiomyocytes were treated with OPG at different concentrations and the cellular hypertrophy was evaluated. Meanwhile, the activity of FAK and other the phosphorylation kinases were detected. Autophagy flux assay was performed in absence and presence OPG. The interaction between proteins was analyses using Co-Immunoprecipitation assay.Results We found that OPG induced cardiomyocyte hypertrophic response, accompanied by dramatic increases a series of inflammatory factors and cytokines, as well as collagen synthesis. Also OPG inhibits autophagy and induces FAK phosphorylation. FAK silencing using si-RNA abrogates the effect of OPG on autophagy and cellular hypertrophy. Furthermore, Co-Immunoprecipitation assay reveals that OPG inhibits autophagy through enhancing the binding of FAK and Beclin1 Tyr 233.Conclusion The FAK/Beclin1 signal pathway is essential for the OPG induced autophagy inhibition and hypertrophic response in cultured H9C2 cells.