Mir-140b-3p调控CD38/NAADP信号通路参与哮喘气道平滑肌细胞自噬、凋亡的机制研究

项目名称： Mir-140b-3p调控CD38/NAADP信号通路参与哮喘气道平滑肌细胞自噬、凋亡的机制研究

项目编号： No.81460005

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 莫碧文

作者单位： 桂林医学院

项目金额： 45万元

中文摘要： 钙信号通过调控气道平滑肌细胞(ASMCs)增殖、凋亡参与哮喘气道重塑。自噬与凋亡在疾病过程中相互影响发生作用，它们在哮喘ASMCs增殖中起何作用？CD38催化底物生成的第二信使分子烟碱酸腺嘌呤二核苷酸磷酸（NAADP）调节细胞内Ca2+释放影响细胞自噬，ASMCs膜广泛表达的CD38是否通过NAADP调控的Ca2+信号参与ASMCs自噬、凋亡？miR-140-3p是否通过调控靶基因CD38的表达，影响NAADP/Ca++信号轴诱导的ASMCs自噬、凋亡？本项目拟通过关键信号分子沉默或增强、自噬诱导剂或抑制剂干预体外培养的ASMCs及慢性哮喘大鼠模型，应用透射电镜、分子生物学技术等检测细胞自噬、凋亡的发生，探讨细胞自噬、凋亡与CD38/NAADP信号通路的关系、Mir-140b-3p调控CD38/NAADP信号通路参与哮喘ASMCs自噬、凋亡的机制，对哮喘气道重塑的发病机制进行了全新的诠释。

中文关键词： 支气管哮喘；气道平滑肌细胞；细胞自噬；微小RNA；CD38

英文摘要： Calcium signal regulate proliferation, apoptosis of airway smooth muscle cells (ASMCs) in airway remodeling in asthma. Autophagy and apoptosis play a different role in the disease process by mutual influence. it is unclear whether autophagy and apoptosis contribute to the proliferation of ASMCs in asthma. CD38 can catalyzed substrate to produce second messenger molecules nicotinic acid adenine dinucleotide phosphate (NAADP), NAADP regulate the release of intracellular Ca2+ involved in autophagy. CD38 is widely expressed in ASMCs, it is unclear whether CD38 regulating NAADP/Ca2+ signal pathway is involved in autophagy and apoptosis in asthmatic airway smooth muscle cells. CD38 is the target gene of miR-140-3p, miR-140-3p regulate the expression of CD38 in airway smooth muscle cells, we hypothesis that Mir-140b-3p regulating CD38/NAADP signal pathway is involved in autophagy and apoptosis in the asthmatic ASMCs. In this study, we will isolate rat ASMCs, Chronic rat asthmatic model will be established, autophagy inducer or autophagy specific inhibitor will be used. then we silence or enhance the expression of the key signaling molecules in ASMCs or rat asthmatic model, autophagy and apoptosis will be detect by transmission electron microscopy or molecular biology technology. We now sought to elucidate that Mir-140b-3p regulating autophagy and apoptosis of ASMCs contributes to airway remodeling of asthma through activated CD38/NAADP signal pathway. It is a completely new interpretation in pathogenesis of asthmatic airway remodeling.

英文关键词： ASTHMA;AIRWAY SMOOTH MUSCLE CELLS;AUTOPHAGY;MICRORNA;CD38