CTNNAL1表达的应答性调控及其信号组装在哮喘及上皮应激中的作用

项目名称： CTNNAL1表达的应答性调控及其信号组装在哮喘及上皮应激中的作用

项目编号： No.30800504

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 向阳

作者单位： 中南大学

项目金额： 20万元

中文摘要： 本项目以本课题组新发现的在哮喘病人表达下调的粘附分子CTNNAL1 (catenin alpha-like 1)作为研究的切入口，探讨其功能意义、调控机制及信号分子组装。项目完成情况如下：①#35777;实CTNNAL1参与气道应激反应，其表达水平在应激的小鼠支气管肺组织及培养的人BEC中均增高；②#37319;用多探针EMSA转录因子谱及染色质免疫共沉淀研究策略，发现LEF-1和AP-2α21442;与臭氧应激状态下支气管上皮细胞内CTNNAL1基因表达调控；③#36827;一步收集哮喘病人和正常人外周血，Real-time PCR 证实了CTNNAL1 在哮喘病人中表达下调，但对DNA启动子区域测序未发现碱基变异位点；④#20813;疫共沉淀检测发现了臭氧应激条件下与CTNNAL1相互作用的一个蛋白HSP90；⑤#20307;外检测CTNNAL1表达对BEC功能的影响，发现CTNNAL1可促进支气管上皮细胞增殖、粘附及损伤修复。本研究初步阐明了CTNNAL1基因表达调控机制及其功能意义，从上皮细胞粘附与应激角度为哮喘发病机制研究提供新的思路和线索。

中文关键词： CTNNAL1； 哮喘；支气管上皮细胞；应激；信号分子

英文摘要： Our study in previous project found that adhesion molecule catenin alpha-like 1(CTNNAL1) was down-regulated in asthma patients. This project plan to explore the expression and regulation mechanism of CTNNAL1 in stressed BEC and the signaling molecule assembly involved in the function of CTNNAL1。Completion of the project are as follows: ①onfirmed that CTNNAL1 expression was response to stress in the airway; ②he nuclear factors involved in induced expression of CTNNAL1 response to stress was screened by electrophoretic mobilityshift assays (EMSA) and chromatin immunoprecipitation (ChIP), the result showed that LEF-1 could be recruited to the CTNNAL1 promoter; ③further confirmed that CTNNAL1 was down-regulated in asthma patients, but no variation site was found in the promoter region of the CTNNAL1 DNA; ④mmunoprecipitation detected HSP90 was interacted with CTNNAL1 in ozone stress conditions; ⑤n vitro expression showed that CTNNAL1 can promote bronchial epithelial cell proliferation, adhesion and damage repair. Our result illustrated CTNNAL1 mechanism of gene regulation and functional significance. This study will provide new ideas for the pathogenesis of asthma research from epithelial cell adhesion and stress, with theoretical innovation and potential applications.

英文关键词： CTNNAL1; bronchial epithelial cells (BEC); asthma; stress; signaling molecule