TRPS1调控角质形成细胞SNAI2基因转录影响再上皮化启动的作用及机制研究

项目名称： TRPS1调控角质形成细胞SNAI2基因转录影响再上皮化启动的作用及机制研究

项目编号： No.81201473

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 戴霞

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 皮肤大面积缺损可致严重残疾甚至死亡，促进创面愈合是创伤修复研究的重要目标。现认为，角质形成细胞（Kc）向间质细胞转化获得移行能力是启动再上皮化、修复创面的关键。前期基因芯片检测显示在急/慢性创面组织中TRPS1及SNAI2基因存在差异表达，两者是调控上皮-间质转化（EMT）的重要转录因子，体外研究显示增强TRPS1表达能显著抑制SNAI2表达；结合有关文献推测：TRPS1在创面修复过程中发挥了重要作用，其机制与直接抑制SNAI2转录后负向调控Kc EMT有关。本研究拟在构建TRPS1过表达/干扰载体的基础上，通过荧光定量PCR、WB、ChIP、荧光素酶检测等技术在细胞水平阐明TRPS1对Kc间质化的影响及其调节SNAI2表达的信号转导机制，同时在动物水平验证TRPS1调控Kc移行在创面愈合中的作用。研究结果有望从EMT角度阐释再上皮化的调控机制，为临床寻找有效促愈方法提供理论依据。

中文关键词： TRPS1；SNAI2；再上皮化；角质形成细胞；上皮间质转化

英文摘要： evere disability and even death could be subsequently initiated by large-area defects of skin. Therefore,to achieve a rapid re-epithelialization and complete healing is a primary goal for wound repair and regeneration researchers. Keratinocytes(Kc) acquiring mobility via epithelial-mesenchymal transition (EMT) is a committed step for priming the re-epithelialization procedure,however, the molecular machanism of EMT has not been fully understood.A DNA microarray analysis of acute and chronic wound epidermis was performed and a series of genes with variable transcription activity were screened out, incluing TRPS1 and SNAI2,which are both pivotal transcriptional regulator involed in EMT. Further research found that with the promotion of TRPS1 in Kc cultured in vitro,SNAI2 expression induced by TGF-β1 could be dramatically inhibited. In combination of whose nature as a transcriptional repressor and analysis of bioinformation softwares, we presume that SNAI2 could be the down-stream target gene that directly repressed by TRPS1,hence EMT in Kc would be negatively regulated, which ultimately resulting in a retardation of re-epithelialization. In order to confirm this presumption, we anticipate to apply realtime fluorescence quantitative PCR, transwell, chromatin immunoprecipitation(ChIP) and luciferase reporter gene

英文关键词： TRPS1；SNAI2；re-epithelialization；kerationcyte；epithelial-mesenchymal transition