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

Yue Li; Siyuan Fan; Lingyao Kong; Zhenxuan Hao; Yanjun Zhou; Jiahong Shangguan; Lu Gao; Mingdan Wang; Yue Kang; Xiangrao Li; Kun Huang; Chao Zhang; Zhibo Liu

doi:10.1016/j.isci.2023.108070

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

iScience. 2023 Sep 28;26(11):108070. doi: 10.1016/j.isci.2023.108070. eCollection 2023 Nov 17.

Authors

Yue Li^{1

2}, Siyuan Fan³, Lingyao Kong¹, Zhenxuan Hao¹, Yanjun Zhou¹, Jiahong Shangguan¹, Lu Gao¹, Mingdan Wang¹, Yue Kang⁴, Xiangrao Li¹, Kun Huang⁵, Chao Zhang⁶, Zhibo Liu^{2

7}

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
² Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
³ Cardiovascular Center, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
⁴ Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁵ Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
⁶ Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
⁷ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Abstract

CD9 is a member of the tetraspanin protein family, which has been widely studied in inflammation and cancer, but not in pathological cardiac hypertrophy. In this study, we found that the expression of CD9 was increased in transaortic constriction (TAC) myocardial tissue. Knockdown of CD9 alleviated damage to cardiac function in the TAC model and reduced heart weight, cardiomyocyte size, and degree of fibrosis, and vice versa. Mechanistically, co-immunoprecipitation results showed that CD9 and GP130 can bind to each other in cardiomyocytes, and knockdown of CD9 can reduce the protein level of GP130 and the phosphorylation of STAT3 in vivo and in vitro, and vice versa. GP130 knockdown reversed the aggravating effects of CD9 on pathological cardiac hypertrophy. Therefore, we conclude that CD9 exacerbates pathological cardiac hypertrophy by regulating the GP130/STAT3 signaling pathway and may serve as a therapeutic target for pathological cardiac hypertrophy.

Keywords: Cardiovascular medicine; Molecular physiology; Pathophysiology.