CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signalling pathway

Abstract

Abstract Pathological myocardial hypertrophy is a common cardiovascular disease that can progress to heart failure. At present, there is no ideal therapeutic drug in clinical practice. This study aimed to find new therapeutic targets for pathological myocardial hypertrophy. CD9 is a member of the tetraspanin protein family which is widely studied in inflammation and cancer, but has not been studied in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 increased in TAC myocardial tissue. Knockdown of CD9 can alleviate the damage of cardiac function in TAC model, and can reduce heart weight, cardiomyocyte size and degree of fibrosis; overexpression of CD9 can aggravate the damage of cardiac function in TAC model, and can increase cardiac weight, cardiomyocyte size and degree of fibrosis. Mechanistically, Co-IP results showed that CD9 and GP130 can bind to each other in cardiomyocytes, knockdown of CD9 can reduce the protein level of GP130 and phosphorylation of STAT3, and overexpression of CD9 can increase the protein level of GP130 and phosphorylation of STAT3 in vivo and in vitro. Knockdown of GP130 reversed the aggravating effect of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signalling pathway and it may serve as a therapeutic target for pathological cardiac hypertrophy.