长链非编码RNA Fendrr对心肌肥厚的作用及机制研究

项目名称： 长链非编码RNA Fendrr对心肌肥厚的作用及机制研究

项目编号： No.81470516

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 唐其柱

作者单位： 武汉大学

项目金额： 73万元

中文摘要： 心肌肥厚是多种心血管疾病发展至心衰的共同病理生理过程，目前尚无根本有效防治措施。近年来研究显示，长链非编码RNA在生物发育、分化和生长中发挥重要作用，其家族成员Fendrr参与了心脏发育和分化调控过程。我们预实验发现：胸主动脉缩窄术后4周，野生型小鼠肥厚心肌组织Fendrr表达明显下降，提示其参与了心肌肥厚过程。但作用及机制未明。本项目组拟用野生型、Fendrr心脏特异性敲除和转基因小鼠构建压力负荷、血管紧张素II和异丙肾上腺素诱导的心肌肥厚在体模型，观察心肌肥厚表型变化，并探讨Fendrr对信号转导、转录调控和胚胎基因重新表达的影响。同时制作沉默或过表达受Fendrr调控的下游靶基因载体，并转染至心脏特异性Fendrr敲除和转基因小鼠乳鼠原代心肌细胞，从离体水平进一步探讨Fendrr在血管紧张素II和异丙肾上腺素诱导心肌细胞肥大中的作用及机制。旨在为心肌肥厚和心力衰竭防治提供新靶点。

中文关键词： 长链非编码RNA；Fendrr；心肌肥厚；基因敲除；转基因

英文摘要： Cardiac hypertrophy is the common pathophysiological process of a wide variety of cardiovascular diseases that ultimately leading to heart failure. However, no effective treatments exist for the process. Recently, it has been confirmed that long noncoding RNA (LncRNA) play an important role in the biological process of development, differentiation and growth. Fendrr, one member of the LncRNA family, was involved in cardiac development and differentiation. Our preliminary data indicated that the expression of lncRNA Fendrr in myocardial tissue is down-regulated significantly after 4 weeks' aortic banding in C57 mice, but its functions and mechanisms in this process remains unclear. We aim to observe phenotype changes in vivo through pressure overload, AngII and ISO induced cardiac hypertrophy in wild type, cardiac specific knock-out and transgenic mice, and explore the effect of LncRNA Fendrr on signal transduction, transcriptional activation and embryonic gene re-expression. In addition, we will construct vectors for silence or over-expression of genes regulated by LncRNA Fendrr to transfect the primary cardiomyocytes isolated from cardiac specific knock-out and transgenic mice , to further search for the role and mechanisms of LncRNA Fendrr on cardiomyocyte hypertrophy induced by AngII and ISO. These studies are designed to find out new target for the prevention and treatment of cardiac hypertrophy and heart failure.

英文关键词： Lnc RNA;Fendrr;Cardiac hypertrophy;Gene knock-out;Transgene