紫外线诱导系统性红斑狼疮DNA甲基化的分子机制研究

项目名称： 紫外线诱导系统性红斑狼疮DNA甲基化的分子机制研究

项目编号： No.81202349

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 张敏

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： 系统性红斑狼疮（SLE）是自身免疫病的原型，目前其病因和发病机制仍然未明，一般认为是遗传因素、环境因素及其交互作用引起免疫异常，最终导致多器官、系统损害。表观遗传学中DNA甲基化水平的改变在SLE发病机制中的起重要作用，且是近年来研究的热点，SLE存在甲基化异常，多种T细胞表面分子高表达与启动子低甲基化有关。已有研究表明，环境因素能够影响DNA甲基化水平，环境因素中紫外线对SLE的影响尤为重要。本课题拟在近期研究基础上，通过检测经不同剂量紫外线照射前后SLE和健康对照CD4+T细胞的DNA甲基化水平，甲基化转移酶mRNA水平和蛋白质水平,甲基化转移酶的活性以及MAPK信号转导的检测，探讨紫外线诱导系统性红斑狼疮DNA低甲基化的分子机制；采用人类全基因组芯片比较紫外线照射前后基因表达谱的变化，检测基因启动子区域CpG岛甲基化情况，为SLE的治疗提供新的靶点和途径。

中文关键词： 系统性红斑狼疮；CD4+T细胞；DNA甲基化；甲基化转移酶；

英文摘要： Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease. At present, the etiology and pathogenesis is still unknown. It is believed that the genetic factor, environmental factors and their interaction cause abnormal immune, eventually leading to multiple systemic organ damage. The level of DNA methylation in epigenetic plays an important role in SLE pathogenesis, and is a research hotspot in recent years. SLE exists abnormal methylation. And high expression of many T cell surface molecules is relevant to the low promoter methylation. Some studies have shown that environmental factors can affect the level of DNA methylation, especially the ultraviolet. On the basis of our previous experiments, in the present study, we aim to explore the molecular mechanisms of DNA hypomethylation of ultraviolet-induced SLE, by test the level of DNA methylation in CD4 + T cells, the methyltransferase enzyme mRNA and protein levels, the methylation transferase activity and the MAPK signal transduction pathway before and after different doses of ultraviolet radiation in SLE and healthy control groups; compare the changes of gene expression profiles before and after ultraviolet irradiation using the human genome chip, and test the gene promoter methylation regional CpG island, to provide a new target and way in the

英文关键词： Systemic lupus erythematosus；CD4+T cells；DNA methylation；DNA methyltransferase；