RIP140在神经元和神经胶质细胞增殖中的作用研究

项目名称： RIP140在神经元和神经胶质细胞增殖中的作用研究

项目编号： No.30872792

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 郭静竹

作者单位： 北京大学

项目金额： 25万元

中文摘要： RIP140（receptor interacting protein of 140kDa， RIP140），是21号染色体上的转录调节相关基因。既往研究提示，该基因的异常表达与神经系统发育和功能有着极为密切的关系。课题组前期研究和国外相关研究显示RIP140在唐氏综合征胎儿和成人脑中的表达量较正常胎儿和成人明显增高。同时，我们的前期研究已证实，RIP140表达缄默可引起小鼠小胶质瘤细胞增殖减慢，提示该基因异常表达可能通过影响神经元和神经胶质细胞的增殖，进而导致智力低下的发生。本研究从模型细胞、原代培养细胞和动物模型三个层次分析RIP140对细胞增殖和凋亡的影响，证明其通过ERK-MAPK通路影响神经细胞增殖和凋亡分子机制，为进一步以干细胞（胚胎干细胞、iPS和神经干细胞为研究对象，从发育生物学的角度，分析RIP140过量表达致DS智力低下发生的分子机制，找寻可能存在的靶向干预位点奠定基础。

中文关键词： RIP140；基因过量表达；神经元；胶质细胞；增殖

英文摘要： RIP140 is 21 of chromosome transcriptional regulation related gene. Previous study suggests, this aberrant gene is closely related to the development of nervous system and function. The earlier stage of our group's study and foreign related study show that RIP140 expression in the fetus and adult of down syndrome is significantly higher than its expression of the normal. At the same time, The earlier stage of our study has confirmed that RIP140 express silence can cause small glioma cell of mice proliferating slowly, suggesting that the aberrant gene expression may cause the occurrence of mental retardation by affecting the neuron and glioma cell's proliferation. Therefore, this study intend to analysis how RIP140 affect cell proliferation and apoptosis from model cell, primary culture cell and animal model three levels ,we proved that RIP140 overexpression promote the proliferation and reduce the apoptosis of cultured cell lines, primary glia and brain tissues. all these results provide us a novel molecular mechanism of DS's mental retardation with RIP140 at Stem cell(ES, iPS and Adult nerve stem cell) levels and further to look for possible targeted intervention sites.

英文关键词： RIP140；gene excessively express；neuron； glioma cell；proliferation