Osteoprotegerin prompts cardiomyocyte hypertrophy via autophagy inhibition mediated by FAK/BECLIN1 pathway.
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, indicated by increased cellular size and protein content per cell. OPG increases the heart/body weight ratio in vivo. 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.


CONCLUSION
The FAK/Beclin1 signal pathway is essential for the OPG induced autophagy inhibition and hypertrophic response in cultured H9C2 cells.
['Zheng|Dezhong|D|', 'Zhang|Mingyu|M|', 'Liu|Tingrong|T|', 'Zhou|Tao|T|', 'Shen|Anna|A|']
D000818:Animals D001343:Autophagy D000071186:Beclin-1 D049108:Cell Enlargement D002460:Cell Line D004305:Dose-Response Relationship, Drug D051417:Focal Adhesion Kinase 1 D006984:Hypertrophy D051379:Mice D008810:Mice, Inbred C57BL D032383:Myocytes, Cardiac D053244:Osteoprotegerin D051381:Rats D015398:Signal Transduction
Osteoprotegerin Cardiomyocyte Hypertrophy Autophagy Focal adhesion kinase