长链非编码RNA在高血压血管重建中的作用及其力学生物学机制

项目名称： 长链非编码RNA在高血压血管重建中的作用及其力学生物学机制

项目编号： No.11202133

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 姚庆苹

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 长链非编码RNA（lncRNA）是基因组非编码序列的转录产物，其本身不编码蛋白质，但对基因表达具有重要的调控作用，在正常生命活动和疾病发生中发挥重要作用。但是，迄今为止，对它的研究刚刚起步。有关lncRNA的研究尚未涉及心血管力学生物学领域。本项目拟利用基因芯片技术，建立自发性高血压大鼠（SHR）与对照大鼠（WKY）主动脉lncRNA差异表达谱，采用生物信息学方法对差异lncRNA进行聚类和分析；利用细胞体外周期性张应变加载模型，研究筛选到的lncRNA在张应变调控VSMCs增殖和迁移中的作用；最后，回归高血压模型，在体条件下检测筛选到的lncRNA对血压及血管重建的影响。本项目应用基因组学、生物信息学、细胞力学和分子生物学等相关学科理论和实验技术，旨在明确lncRNA在高血压血管重建中的作用及其力学生物学机制，为阐明高血压血管重建的发病机理和药物治疗靶标的研究提供新的力学生物学依据。

中文关键词： 长链非编码RNA；高血压；张应力；血管平滑肌细胞；增殖

英文摘要： Long noncoding RNA (lncRNA) are the least well-understood products of transcription from genomes. They do not encode proteins. However, recent explosion in knowledge demonstrating the importance of lncRNA in the regulation of multiple major biological processes impacting on normal life activities and disease have brought these heretofore neglected molecular players to forefront. Although new lncRNA are being discovered at a rapid pace, the contributions of lncRNA to cardiovascular mechanobiology remain largely unknown. In this project, first, the genetic differences map of lncRNAs between spontaneously hypertensive rats (SHR) and wistar kyoto rats (WKY) is created by gene chip. And then the obtained data are clustered and analyzed by using bioinformatics method. In the second step, the role of the screened lncRNA in regulation of proliferation and migration in VSMCs subjected to cyclic mechanical strain by Flexcell-4000 is studied. Finally, the new screened lncRNA is knocked down in SHR by RNAi in vivo, leading to identification of its role in vascular remodeling. With the employment of recent advances in technologies, i.e. gene chip、bioinformatics method、mechanical cell biology and molecular biology, the project will achieve successes in illuminating the role of lncRNA in hypertension-induced vascular remodelin

英文关键词： long noncoding RNA；hypertension；mechanical stretch；vascular smooth muscle cells；proliferation