MiRNA调控COPD大鼠肺泡巨噬细胞TLR2受体表达的作用机制研究

项目名称： MiRNA调控COPD大鼠肺泡巨噬细胞TLR2受体表达的作用机制研究

项目编号： No.81200025

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 徐虹

作者单位： 广州军区广州总医院

项目金额： 23万元

中文摘要： 慢性阻塞性肺病（COPD）患者曲霉易感性增高，具体机制尚未阐明。肺泡巨噬细胞（AM）通过TLR2等模式识别受体识别并清除曲霉孢子，在曲霉防御中发挥重要作用；miRNA能通过调节TLRs的表达及信号通路的活化调控免疫效应过程，烟雾暴露影响肺组织中多种miRNAs的表达；另本项目组前期研究发现，COPD大鼠AM在孢子刺激后表面TLR2受体不能正常表达上调，吞噬曲霉孢子及释放炎症因子的能力下降。据此推测：某个/些miRNA(s)可能通过调控AM表面TLR2受体表达，影响COPD大鼠AM对曲霉的防御功能。本课题拟利用miRNA芯片技术测定COPD与正常大鼠AM中差异表达的miRNAs，通过生物信息学分析筛选可能参与TLR2受体表达调控的目标miRNA(s)，用定位点突变、增加或抑制miRNA表达等方法阐明miRNA对TLR2受体表达调控的影响机制，探索吸烟影响AM曲霉防御功能的分子机理。

中文关键词： 肺疾病；阻塞性；慢性；微小RNA；TLR2

英文摘要： COPD patients are more susceptible to Aspergillus and mechanisms underling these phenomena are poorly understood. Alveolar macrophages play an important role in preventing Aspergillus invasion. Through pathogen recognition receptors such as TLR2, alveolar macrophages are able to recognize conidia and then clear them. MiRNAs can regulate immune reaction process by regulating the expression of TLRs and activation of related signal pathways. Research has found that exposure to cigarette smoke can lead to alterations in miRNAs of lung. Our previous study showed that TLR2 protein expression is failed to increase with the stimulation of Aspergillus conidia in COPD rats. The phagocytic function of alveolar macrophages is impaired in COPD rats and the release of inflammatory factors is also not as high as normal rats. We speculate that miRNA can regulate the expression of TLR2 and then affect the AM defense function to Aspergillus in COPD rats. In the present study, MiRNA array will be used to determine the miRNA profile alternation of alveolar macrophage in COPD rats. Bioinformational approaches will be used to identify miRNAs that might target TLR2. We will clarify the mechanism of miRNA regulating the expression of TLR2 with the methods of point mutations, increase or inhibit the expression of target miRNA(s). The ai

英文关键词： Chronic obstructive pulmonary disease；microRNA；Rat；Alveolar macrophages；Toll-like receptor 2