Activated CD4+ T cells-derived exosomal miR-142-3p boosts post-ischemic ventricular remodeling by activating myofibroblast
Lidong Cai, Chao Gong, Weifeng Li, Jumo Zhu, Fangfang Li, Baozhen Qi, Yong Wei, Songwen Chen, Genqing Zhou, Xiaofeng Lu, Juan Xu, Xiaoyu Wu, Guangjian Fan, Jun Li, Shaowen Liu
Abstract
T cells (CD4-activated Exos) evoked pro-fibrotic effects of cardiac fibroblasts, and their delivery into the heart aggravated cardiac fibrosis and dysfunction post-infarction. Mechanistically, miR-142-3p that was enriched in CD4-activated Exos recapitulated the pro-fibrotic effects of CD4-activated Exos in cardiac fibroblasts, and vice versa. Furthermore, miR-142-3p directly targeted and inhibited the expression of Adenomatous Polyposis Coli (APC), a negative WNT signaling pathway regulator, contributing to the activation of WNT signaling pathway and cardiac fibroblast activation. Thus, CD4-activated Exos promote post-ischemic cardiac fibrosis through exosomal miR-142-3p-WNT signaling cascade-mediated activation of myofibroblasts. Targeting miR-142-3p in CD4-activated Exos may hold promise for treating cardiac remodeling post-MI.