MALAT1与 miR-146a相互作用对 EndMT及心肌纤维化的影响及其机制研究

内皮间质转化（EndMT）是促进心肌纤维化（CF）的重要因素。Smad2/3/4是介导CF中EndMT的关键蛋白。MALAT1和miR-146a是高表达于内皮细胞的非编码RNA。前者可促进上皮-间质转化及内皮细胞迁移而后者则被证实可抑制间质细胞表型转变、抑制Smad2/3/4并改善胶原代谢，但两者与EndMT关系均不清楚。我们前期研究发现，MALAT1促进EndMT而miR-146a则抑制EndMT，且两者在内皮细胞呈反向表达。生物信息学分析显示两者可能相互结合并彼此抑制。因此，本研究使用人主动脉内皮细胞和内皮示踪转基因小鼠，明确MALAT1和miR-146a在EndMT中的作用；通过上调或下调miR-146a及Smad2/3/4证实两者在介导MALAT1促EndMT中的作用。并通过一系列方法阐明MALAT1与miR-146a交互作用的机制，为CF的防治提供新的思路和理论依据。

Endothlial-mesenchymal transition, EndMT promotes cardic fibrosis (CF). Smad2, Smad3 and Smad4, which are the effector molecular of TGF-β signaling pathway in the process of EndMT, are the key proteins during EndMT in CF. lncRNA MALAT1 and miR-146a highly express in endothelial cells and play an important role in endothelial functions. MALAT1 promotes epithelial-mesenchymal transition, which share similar mechanisms of EndMT, and miR-146a has been proven to play a protective role in mesenchymal transition, inhibit Smad2/3/4 and improve collagen metabolism. Relationship among MALAT1, miR-146a and EndMT are unknown. Our pre-experiment showed that MALAT1 promoted EndMT and miR-146a inhibited this process. Moreover, MALAT1 and miR-146a have a reversely expression pattern. The "Starbase" predictive formula show a binding structure between MALAT1 and miR-146a and a possibility that MALAT1 and miR-146a inhibit each other. Therefore, we aim to demonstrate the effects of MALAT1 in the EndMT and CF, and elucidate the roles of miR-146a and Smad2/3/4 in this process using human aortic endothelial cells and Tie2-lacZ mice, which facilitate endothelium tracking. Besides, we sought to explore the regulatory effects between MALAT1 and miR-146a. Our program will provide more mechanisms of EndMT and CF, which might give more information in clinical practice.