CD9, a member of the tetraspanin protein family, has diverse biological functions including cell adhesion, motility, metastasis, growth, signal transduction, and differentiation [4]. It is involved in multiple associated pathways and is of great biological importance in various physiological and pathological conditions, such as its role in intercellular communication through extracellular membrane vesicles [1]. Genetic models, like KO or CKO mouse models, are valuable for studying CD9's functions.

In a transaortic constriction (TAC) mouse model, knockdown of CD9 alleviated damage to cardiac function, reduced heart weight, cardiomyocyte size, and fibrosis. Mechanistically, CD9 binds to GP130 in cardiomyocytes, and knockdown of CD9 reduces the protein level of GP130 and phosphorylation of STAT3, suggesting CD9 exacerbates pathological cardiac hypertrophy through regulating the GP130/STAT3 signaling pathway [2]. In another study, deficiency of CD9 in the liver of mice exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism, indicating CD9 counteracts liver steatosis [3].

In conclusion, CD9 plays crucial roles in multiple biological processes. Model-based research, especially through KO mouse models, has revealed its functions in pathological cardiac hypertrophy and liver steatosis. Understanding CD9's functions provides potential therapeutic targets for these diseases.

References:

1. Lorico, Aurelio, Lorico-Rappa, Marco, Karbanová, Jana, Corbeil, Denis, Pizzorno, Giuseppe. 2021. CD9, a tetraspanin target for cancer therapy? In Experimental biology and medicine (Maywood, N.J.), 246, 1121-1138. doi:10.1177/1535370220981855. https://pubmed.ncbi.nlm.nih.gov/33601913/

2. Li, Yue, Fan, Siyuan, Kong, Lingyao, Zhang, Chao, Liu, Zhibo. 2023. CD9 exacerbates pathological cardiac hypertrophy through regulating GP130/STAT3 signaling pathway. In iScience, 26, 108070. doi:10.1016/j.isci.2023.108070. https://pubmed.ncbi.nlm.nih.gov/37860696/

3. Zheng, Yi, Wang, Yuren, Xiong, Xin, Qu, Hua, Zheng, Hongting. 2024. CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2400819. doi:10.1002/advs.202400819. https://pubmed.ncbi.nlm.nih.gov/38837628/

4. Brosseau, Carole, Colas, Luc, Magnan, Antoine, Brouard, Sophie. 2018. CD9 Tetraspanin: A New Pathway for the Regulation of Inflammation? In Frontiers in immunology, 9, 2316. doi:10.3389/fimmu.2018.02316. https://pubmed.ncbi.nlm.nih.gov/30356731/