Effect of fibroblasts small- conductance Ca2+ -activated potassium channel subtype 2 (SK2) on myocardial fibrosis in pressure overload mouse

• Published in: Cellular signalling Vol. 124; p. 111401
• Main Authors: Chen, Yihan, Bao, Limeng, Dong, Fengjuan, Xv, Menru, Li, Weidong, Luo, Tianxia, Xing, Chenxv, Yan, Ningning, Niu, Kangli, Zhang, Ningyuan, Fan, Hongkun
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2024
• Subjects: Fibroblasts; Myocardial fibrosis; SK2 channel; TAC; TGF β signaling pathway; Fibroblasts; TGF β signaling pathway; Myocardial fibrosis; SK2 channel; TAC
• ISSN: 0898-6568; 1873-3913; 1873-3913
• DOI: 10.1016/j.cellsig.2024.111401

Studies have shown that Small conductance Ca2 + −activated K+ (SK) channel are expressed in fibroblasts. We aimed to determine the expression of SK2 channels in cardiac fibroblasts during myocardial hypertrophy and investigate its relationship with fibrotic remodeling. Myocardial hypertrophy and fibrotic remodeling induced by transverse aortic constriction (TAC) were assessed by echocardiography, Masson's trichrome staining and Western blot. Knockdown and overexpression of the SK2 protein were used to assess relationship between SK2 expression in fibroblasts and myocardial fibrosis. There is a positive correlation between myocardial fibrosis and SK2 channel protein expression during the development of myocardial hypertrophy. The differentiation and secretion of fibroblasts in mice with cardiac hypertrophy are enhanced, and the expression of SK2 channel protein is increased. Manipulating SK2 levels in fibroblasts can either promote or inhibit their differentiation and secretory function. Knocking down SK2 reduces the up-regulation of TGF β1, p-Smad2/3/GAPDH, p-p38/GAPDH, p-ERK1/2/GAPDH, and p-JNK/GAPDH proteins induced by Ang II in cardiac fibroblasts without significantly affecting total protein levels. AAV9-SK2-RNAi injection in mice improves cardiac function. Collectively, our study suggests that the expression of the SK2 channel is significantly increased in fibroblasts of mice with myocardial hypertrophy, potentially impacting myocardial fibrosis remodeling via the TGF-β signaling pathway. •We investigated the changes in SK2 channel expression in TAC induced cardiac hypertrophy and the effect of SK2 expression in fibroblasts on myocardial fibrosis and its potential mechanism.