Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, No.183, West Zhongshan Ave, Tianhe District Guangzhou, 510630 Guangzhou, Guangdong, China; Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.
Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, No.183, West Zhongshan Ave, Tianhe District Guangzhou, 510630 Guangzhou, Guangdong, China; Key Laboratory for Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.
Life Sci. 2021 Jan 1;264:118550. doi: 10.1016/j.lfs.2020.118550. Epub 2020 Oct 6.
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.
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.
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.
The FAK/Beclin1 signal pathway is essential for the OPG induced autophagy inhibition and hypertrophic response in cultured H9C2 cells.
有报道称骨保护素（OPG）可诱导心肌细胞肥大，但具体机制尚不清楚。本研究旨在探讨黏着斑激酶（FAK）通路在 OPG 诱导培养的心肌细胞肥大中的作用。
用不同浓度的 OPG 处理大鼠心肌细胞系 H9C2，评估细胞肥大程度。同时，检测 FAK 及其它磷酸化激酶的活性。在有无 OPG 的情况下进行自噬流检测。采用免疫共沉淀法分析蛋白间的相互作用。
我们发现 OPG 诱导心肌细胞发生肥大反应，表现为细胞体积增大和细胞内蛋白含量增加。OPG 增加体内心脏/体重比。此外，OPG 抑制自噬并诱导 FAK 磷酸化。使用 siRNA 沉默 FAK 可消除 OPG 对自噬和细胞肥大的作用。进一步的免疫共沉淀实验表明，OPG 通过增强 FAK 和 Beclin1 的结合来抑制自噬。
FAK/Beclin1 信号通路是 OPG 诱导培养的 H9C2 细胞自噬抑制和肥大反应所必需的。
