CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway.
CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway.
复制标题
DOI：
10.1016/j.isci.2023.108070
复制
发表时间：
2023-11-17
期刊：
影响因子：
5.8
通讯作者：
Liu, Zhibo
中科院分区：
文献类型：
--
作者：
Li, Yue;Fan, Siyuan;Kong, Lingyao;Hao, Zhenxuan;Zhou, Yanjun;Shangguan, Jiahong;Gao, Lu;Wang, Mingdan;Kang, Yue;Li, Xiangrao;Huang, Kun;Zhang, Chao;Liu, Zhibo
CD9是Tetraspanin蛋白家族的一员，已被广泛研究在炎症和癌症中，但在病理性心肌肥厚中尚未见报道。在本研究中，我们发现CD9在TAC心肌组织中的表达增加。在TAC模型中，CD9基因敲除减轻了对心脏功能的损害，减轻了心脏重量、心肌细胞大小和纤维化程度，反之亦然。从机制上讲，免疫共沉淀结果表明CD9和gp130在心肌细胞中可以相互结合，CD9的敲除可以降低体内外gp130的蛋白水平和STAT3的磷酸化水平，反之亦然。Gp130基因敲除可逆转CD9对病理性心肌肥厚的加重作用。因此，我们认为CD9通过调节gp130/STAT3信号通路而加重病理性心肌肥厚，可作为治疗病理性心肌肥厚的靶点。TAC心肌组织CD9表达上调CD9表达下调可减轻TAC诱导的病理性心肌肥厚，反之亦然。CD9通过调节gp130/STAT3调节心血管药物；病理生理学；分子生理学
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. The expression of CD9 increased in TAC myocardial tissue Knockdown of CD9 alleviated TAC-induced pathological cardiac hypertrophy, and vice versa CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 Cardiovascular medicine; Pathophysiology; Molecular physiology
登录
查看更多内容
DOI：
10.1073/pnas.92.11.4862
发表时间：
1995-05-23
影响因子：
11.1
作者：
HIROTA, H;YOSHIDA, K;TAGA, T
通讯作者：
TAGA, T
影响因子：
9.3
作者：
Yamauchi-Takihara, K;Kishimoto, T
通讯作者：
Kishimoto, T
影响因子：
12.4
作者：
Shi, Yu;Zhou, Wenchao;Bao, Shideng
通讯作者：
Bao, Shideng
影响因子：
7.3
作者：
Brosseau C;Colas L;Magnan A;Brouard S
通讯作者：
Brouard S
影响因子：
2.7
作者：
Rouger-Gaudichon, Jeremie;Cousin, Elie;Gandemer, Virginie
通讯作者：
Gandemer, Virginie