ErbB信号通路基因GAB1、EPS15异常表达与心肌细胞凋亡及心脏发育异常的相关性研究

项目名称： ErbB信号通路基因GAB1、EPS15异常表达与心肌细胞凋亡及心脏发育异常的相关性研究

项目编号： No.31301145

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 苏冬梅

作者单位： 国家人口计生委科学技术研究所

项目金额： 22万元

中文摘要： 心肌细胞的异常凋亡与先天性心脏病发生密切相关，临床研究表明母亲妊娠期糖尿病是儿童先天性心脏病发生的病因之一, 主要原因可能由于高糖诱导心肌细胞过度凋亡导致胎儿心脏发育异常,但其具体致病机制仍不很清楚。我们课题组建立了高糖诱导的人心肌细胞凋亡模型，通过表达谱基因芯片技术,筛选出364个差异表达基因，生物信息学分析发现ErbB通路相关基因GAB1和EPS15在凋亡心肌细胞中表达异常。本项目拟在此基础上深入研究GAB1和EPS15及ErbB/PI3K等通路在高糖诱导心肌细胞凋亡中的作用机制，并建立高血糖妊娠大鼠模型，进一步明确GAB1和EPS15异常表达与胚胎心脏发育异常的相关性。本课题从心肌细胞的转录基因组筛选出与心肌细胞凋亡相关的GAB1和EPS15等一系列基因，并深入研究其作用机制，为高糖引起心肌细胞凋亡进而影响心脏发育提供了新的实验基础，也为先天性心脏病致病机制研究，提供新理论依据。

中文关键词： 高糖环境；细胞凋亡；先天性心脏病；基因表达；信号转导

英文摘要： Excessive cardiomyocyte apoptosis is related directly to the onset of congenital heart disease. Diabetes mellitus in pregnancy is one of the maternal diseases that cause congenital birth defects in infants. Excessive cardiomyocyte apoptosis induced by hyperglycemia plays a critical role in cardiac malformations. However, the underlying molecular mechanism remains unknown. In our study, we analyzed genome-wide expression profiling in the cardiomyocytes treated with or without high-glucose. Microarray analysis revealed that a total of 364 genes changes in mRNA expression. Further bioinformatics analysis revealed that some of genes which involved in ErbB signaling pathway such as GAB1 and EPS15 were differently expressed in apoptotic cardiomyocyte. Based on our finding and related studies, we intend to perform further research on the molecular mechanism of GAB1 and EPS15 on high-glucose induced cardiomyocyte apoptosis. Furthermore, pregnant Rats with diabetic mellitus were generated to investigate the association between abnormal expression of ErbB/PI3K signaling pathway related genes and cardiac malformations. In conclusion, our study discovered a series of novel genes that related with apoptosis from genome-wide expression profiling of cardiomyocyte. We also investigated the detailed molecular mechanism in cardio

英文关键词： high glucose；apoptosis；Congenital heart disease；gene expression；signal transduction