长链非编码RNA MEG3激活p53参与病理性心肌肥厚中内皮损伤的作用和机制

项目名称： 长链非编码RNA MEG3激活p53参与病理性心肌肥厚中内皮损伤的作用和机制

项目编号： No.81500210

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈峰

作者单位： 中国人民解放军第二军医大学

项目金额： 17万元

中文摘要： 心肌肥厚是心脏适应压力负荷的一种代偿机制，如何延缓心肌肥厚到心力衰竭的进展是我们目前亟需解决的重要问题。病理性心肌肥厚中血管损伤和功能不全是导致其向心力衰竭发展的重要原因，但其具体机制目前尚未阐明。长链非编码RNA作为一种新的转录本调节各种病理生理过程。我们前期通过深度测序对内皮细胞中lncRNA进行了检测，发现MEG3调控内皮细胞生长和迁移能力，且抑制MEG3水平明显影响p53的表达。基于p53信号通路在血管损伤中的重要作用，我们提出科学假设：lncRNA MEG3可通过激活p53调控内皮细胞生长，参与调控病理性心肌肥厚中血管损伤的作用和机制。我们拟分别在细胞、动物水平，综合利用基因干预、共聚焦显微成像、基因芯片等手段研究MEG3调控内皮细胞功能的作用机制，旨在阐明病理性心肌肥厚中血管损伤的调控机制。研究成果将丰富血管损伤的调控网络，为心肌缺血损伤的治疗以及延缓心衰提供新的研究

中文关键词： 长链非编码RNA；心肌肥厚；内皮损伤；MEG；3；p53

英文摘要： Myocardial hypertrophy is a compensatory response of heart to pressure overload, and how to delay the progression to heart failure is an important problem we need solve currently. The vascular injury and dysfunction in pathological myocardial hypertrophy are important causes leading to the heart failure, and the mechanism had not been clarified yet. As a new transcripts, long noncoding RNA was proved to regulate various pathological and physiological process. Previously, we detected the expression of lncRNA in endothelial cells by deep sequencing. We found that MEG3 regulated endothelial cell growth and migration, and inhibition of MEG3 significantly reduced p53 signal pathway. Therefore, the hypothesis is proposed: The long non-coding RNA MEG3 participate in the regulation of vascular injury in pathological myocardial hypertrophy by activating p53 to promote endothelial cells growth. We plan to study the function of MEG3 by gene intervention, confocal imaging and gene chip technology on endothelial cells and animal levels, so as to clarify the mechanism of vascular injury in pathological myocardial hypertrophy. The research results will expand the regulation network of vascular injury and repair, and provide a new approach to treatment of myocardial ischemia injury and delay heart failure.

英文关键词： long non-coding RNA;myocardial hypertrophy ;endotherial injury ;MEG 3;p53