ADAM33在维吾尔族人群哮喘气道血管重塑中的作用和分子机制

支气管哮喘气道重塑的发生先于临床症状的出现，气道血管的再生与重塑是气道重塑的主要特征，其机制有待阐明。ADAM33是人类新近发现，已被确定为哮喘的易感基因。课题组研究发现：ADAM33基因存在与维吾尔族哮喘人群相关的SNPs和易感性或保护性的单体型；T细胞因子IL-4、IL-13和INF-γ可能通过调控ADAM33表达影响气道血管重塑。但是ADAM33基因异常表达对气道血管所产生的影响和分子机制（信号途径），迄今国内外尚无报道。本研究拟将已证实哮喘发病与ADAM33基因突变相关的维吾尔族患者的临床资料引入到研究中，在原代培养的哮喘患者气道血管内皮/平滑肌细胞中观察ADAM33对气道血管重塑（细胞增殖、凋亡、迁移等）的影响作用和信号传导通路，以及T细胞因子对ADAM33基因表达的调控机制，并在哮喘患者临床数据中验证ADAM33与气道重塑严重程度、肺功能的关系和分子机制，为哮喘防治提供新思路。

Asthmatic airway remodeling occurs prior to clinical symptoms, the airway vascular regeneration and remodeling is the principal characteristics of airway remodeling, while the mechanism is unknown. ADAM33 is newly found and had been recognized as the susceptible gene of asthma. Our research team found that ADAM33 gene has SNPs and susceptible or protective haplotype related to Uighur asthmatic patients; T-cytokines IL-4, IL-13 and INF-γ may influence the airway vascular remodeling by regulate the expression of ADAM33 gene. But the influence and its molecular mechanism (signal pathway) of ADAM33 anomaly expression to airway vessel had not been reported worldwide yet. Our study intended to adopt the clinical data which had been confirmed among Uighur patients that the pathogenesis of asthma did have relationship with the ADAM33 gene mutation, observe the regulate effect of ADAM33 and signal transduction pathway on airway vascular remodeling (proliferation, apoptosis and motility) in the primary cultured asthmatic airway vascular endothelial/smooth muscle cell and how the T-cytokines regulate the expression of ADAM33 gene. To verify the relationship and the molecular mechanism between ADAM33 and the the severity degree of airway vascular remodeling and lung function, provide a new project in the prevention and treatment of asthma.