石英致肺纤维化的表观遗传改变及与细胞增殖信号转导通路关系的研究

项目名称： 石英致肺纤维化的表观遗传改变及与细胞增殖信号转导通路关系的研究

项目编号： No.81472956

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： 叶萌

作者单位： 中国疾病预防控制中心职业卫生与中毒控制所

项目金额： 90万元

中文摘要： 石英粉尘（简称石英）是我国最主要的职业危害因素之一。表观遗传学及miRNA的研究飞速发展，为石英毒性研究提供了新的生长点。本课题组已证明石英可致肺组织甲基化水平改变，PPAR、PTEN、JAK、STAT受到DNA甲基化水平改变的调控。本研究采用独特的尘肺病患者肺组织样本，采取现场人群与实验室研究相结合的方法。利用高通量芯片技术，辅以特异基因的DNA甲基化水平、特异miRNA检测，多层次、多水平研究职业石英暴露与健康效应的关系，寻找暴露人群早期健康损害的特征性生物标志物。采用RNAi等分子生物学技术，探索PPAR、PTEN、JAK、STAT等信号分子是否参与了石英诱导的信号通路的活化，证实其上下游关系及DNA甲基化和特异miRNA水平改变在其中的作用。本题思路新颖，所提假说层次清晰。将为深入探讨尘肺病发病机制，为早期预警、预测，筛查有效健康监测指标，保护高危敏感人群提供重要的科学依据。

中文关键词： 石英；纤维化；表观遗传学；细胞增殖；信号转导通路

英文摘要： Silica is one of the most important occupational harmful factors in China. The fast developments of epigenetic and miRNA provide a new growing point for the toxicity study of silica. Our group has shown changes of methylation levels induced by silica in lung, and PPAR, PTEN, JAK, STAT is regulated by alterations of DNA methylation levels. The special lung tissue of silicosis was used in this study. The investigations of factories and laboratory researches were combined. Using high-throughput microarray technology, the level of DNA methylation, miRNA detection of special gene, relationship between exposure and health effects of occupational silica exposur were studied in multiple levels to find the characteristic biomarkers of early health damages. Using RNAi and other molecular biological techniques, we explore whether PPAR, PTEN, JAK and STAT was involved in the activaty of signal pathway induced by silica, confirm the relationship between upstream and downstream and DNA methylation and special miRNA level changes. This study is novel and the hypothesis is clear. It will provide provide important scientific basis for further mechanism studies of silicosis, early warning, forecasting, screening effective health monitoring, protecting the risk sensitive people.

英文关键词： silica;silicosis;epigenetic;cell proliferation;signal pathway