Osteoprotegerin prompts cardiomyocyte hypertrophy via autophagy inhibition mediated by FAK/BECLIN1 pathway

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 trea...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2021-01, Vol.264, p.118550, Article 118550
Main Authors: Zheng, Dezhong, Zhang, Mingyu, Liu, Tingrong, Zhou, Tao, Shen, Anna
Format: Article
Language:English
Subjects:
Animals
Assaying
Autophagy
Autophagy - drug effects
Autophagy - physiology
Beclin-1 - metabolism
Biomedical materials
Body weight
Cardiomyocyte
Cardiomyocytes
Cell Enlargement - drug effects
Cell Line
Dose-Response Relationship, Drug
Focal adhesion kinase
Focal Adhesion Kinase 1 - metabolism
Hypertrophy
Immunoprecipitation
Kinases
Mice
Mice, Inbred C57BL
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Osteoprotegerin
Osteoprotegerin - pharmacology
Phagocytosis
Phosphorylation
Proteins
Rats
RNA-mediated interference
Signal Transduction - drug effects
Signal Transduction - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2020.118550