E3泛素连接酶CUL4A在COPD小气道上皮细胞间质转化中的作用机制研究

项目名称： E3泛素连接酶CUL4A在COPD小气道上皮细胞间质转化中的作用机制研究

项目编号： No.81500029

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王琴

作者单位： 山东大学

项目金额： 18万元

中文摘要： 慢性阻塞性肺疾病(COPD)是呼吸系统的常见病和多发病，目前尚没有有效的防治手段。气流受限与COPD的临床严重程度显著相关，而小气道壁增厚是COPD气流受限的主要原因之一。近期研究发现上皮间质转化（EMT）是导致COPD小气道壁增厚的重要因素。我们前期研究发现CUL4A在COPD患者的小气道上皮细胞中过表达；CUL4A的表达水平高低与COPD小气道上皮细胞的EMT发生呈显著正相关；香烟提取物能够促进小气道上皮细胞CUL4A过表达。这些预实验结果提示CUL4A对于COPD小气道上皮细胞EMT发生可能具有调控作用。本研究试图明确CUL4A参与调控COPD小气道上皮细胞EMT的发生；研究CUL4A调控小气道上皮细胞发生EMT的相关分子机制；明确CUL4A调控小气道上皮细胞EMT的关键分子的作用，并寻找有效的干预措施，从而深入阐明COPD气道重塑的机制，为其有效防治提出新的靶点。

中文关键词： 慢性阻塞性肺疾病；小气道上皮细胞；上皮间质转化

英文摘要： Thicken small airway wall is the main cause of irreversible airflow limitation characteristic in COPD, which is significantly related to the severity of COPD. Myofibroblast around small airway play a key role in the process of thicken small airway wall. Myofibroblast is partly from epithelial to mesenchymal transition (EMT). Our previous study showed that the EMT process was obviously present in small airway epithelium of patients with COPD. We indicated that the level of CUL4A was significantly elevated in COPD patients compared to control group in small airway epithelium, and the expression of CUL4A in small airway epithelium was significantly related to EMT. Taken together with previous reports, we postulate that CUL4A may play an important role in the process of EMT of small airway epithelium.To test our hypothesis, we planned to: clarify that CUL4A participate in the EMT of small airway epithelium in COPD; explore the possible signal transduction mechanism of EMT induced by CUL4A in small airway epithelium; verify the role of signal transduction factor in EMT induced by CUL4A in small airway epithelial cells. These will further help us understand the pathogenesis of COPD, and will shed new lights on prevention and treatment of COPD.

英文关键词： COPD;small airway epithelium cell;EMT