MiR-181b Targets Semaphorin 3a to Mediate TGF-β-induced Endothelial to Mesenchymal Transition: Implication in Atrial Fibrillation. MiR-181b Targets Semaphorin 3a to Mediate TGF-β-induced Endothelial to Mesenchymal Transition: Implication in Atrial Fibrillation

Background:This study investigated if and how atrial endothelial cells may transform to mesenchymal cells and contribute to atrial fibrosis via endothelial-to-mesenchymal transition (EndMT). Results:We show a novel mechanistic link between TGF-β1/SMAD signaling and decreased Sema3a expression through the induction of miR-181b; this pathway plays an important role in EndMT associated with the pathogenesis of AF. Both miR-181b and Sema3a are potential therapeutic targets in AF. Overall design: The AAECs were isolated from 3 patients and were treated TGFbeta(5ng/mL) for 24hr to mimic the pathogenesis and performed miRNA arrays

背景：本研究旨在探讨心房内皮细胞是否可通过内皮-间充质转化（Endothelial-to-Mesenchymal Transition, EndMT）转化为间充质细胞，并经由该过程参与心房纤维化的发生，同时阐明其具体分子机制。结果：本研究揭示了一条全新的机制通路：转化生长因子-β1/SMAD（TGF-β1/SMAD）信号通路可通过诱导miR-181b的表达，下调Sema3a的转录水平；该通路在与心房颤动（Atrial Fibrillation, AF）发病机制相关的EndMT过程中发挥关键调控作用。miR-181b与Sema3a均可作为心房颤动的潜在治疗靶点。实验设计：从3名患者体内分离心房内皮细胞（AAECs），以5ng/mL的转化生长因子-β（TGF-β）处理24小时以模拟疾病病理进程，随后开展microRNA芯片检测。