YKL-40是人体内表达的一种甲壳酶样蛋白，在炎症和组织重构中发挥重要作用，近年来证实其与哮喘之间存在密切相关性，但具体机制不明。气道重构是哮喘重要的病理学特点，涉及的机制研究目前主要集中在①上皮-间质转化（EMT）②气道平滑肌细胞（ASMC）的增殖、迁移和抗凋亡③细胞外基质（ECM）的降解-沉积失衡三个方面。本项目的研究目的就是阐明YKL-40能否通过这三个方面的机制诱导哮喘气道重构的发生，即①能否直接诱导人支气管上皮细胞发生EMT；②能否通过细胞周期相关途径诱导ASMC增殖、通过FAK-Src和MAPK途径诱导ASMC迁移、以及通过Caspase途径诱导ASMC抗凋亡；③能否通过调节ASMC分泌MMP和TIMP从而介导ECM的降解-沉积失衡。通过研究，我们可以揭示YKL-40介导哮喘气道重构的具体机制，从中寻找能阻止或逆转哮喘气道重构的有效干预靶点，为哮喘的治疗提供新的方向和思路。

YKL-40 is a chitinase-like protein which has been demonstrated to have an important role in inflammation and remodeling. Recently, YKL-40 has been reported to be closely associated with asthma; however, the underlying mechanisms remain to be elucidated. As is known to all, the airway remodeling is a key feature of pathophysiologic changes in asthma, which involves a wide array of structural alterations. Epithelial injury including epithelial mesenchymal transition (EMT), an increased airway smooth muscle mass due to proliferation, migration and anti-apoptosis of airway smooth muscle cells, and subepithelail fibrosis induced by enhanced deposition of extracellular matrix proteins, are three major aspects of airway remodeling in asthma. The aim of this study is to investigate whether YKL-40 could lead to airway remodeling in asthma through these three mechanisms. We will make it clear that whether YKL-40 could induce EMT, increase airway smooth muscle mass through activation of cell cycle, FAK-Src, MAPK and Caspase signaling pathways, and result in subepithelial fibrosis by regulating the actions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We are expecting to identify some mechanisms involving the airway remodeling of asthma, and find some candidate molecules or targets to prevent from or reverse the airway remodeling in order to provide new lights on treatment of asthma.