屋尘螨（HDM）是哮喘发病最常见的过敏原，可以增高气道上皮内钙离子浓度（[Ca2+]i）、破坏上皮屏障功能，加重气道高反应性。我们的前期研究证实非选择性阳离子通道TRP通过调节[Ca2+]i，参与调控平滑肌细胞迁移、增殖、重塑及收缩。本课题进一步探讨TRPV4 通道介导的气道上皮功能失调在HDM哮喘中的作用，研究拟从如下几方面开展：（1）探索HDM对气道上皮TRPV4表达的影响及通道功能的改变，验证TRPV4介导的钙内流是HDM致上皮[Ca2+]i升高的主要途径；（2）明确TRPV4对HDM所致上皮膜电阻和连接蛋白改变、炎症因子分泌的调控作用；（3）构建HDM哮喘模型，在整体水平确认TRPV4在HDM哮喘上皮通透性改变、气道炎症、气道高反应性和气道重塑中的地位。本项目将阐明气道上皮TRPV4通道在HDM所致哮喘中扮演的关键角色，为有效防治哮喘提供新思路，为开发哮喘治疗新药提供有力依据。

House dust mites （HDM）has been well-recognized as the leading allergen for asthma. Recent findings demonstrated HDM stimulation resulted in elevation of intracellular calcium（[Ca2+]i）, disruption of epithelial barrier function as well as exacerbation of airway hyper-responsiveness (AHR). We have previously shown TRPs, serving as non-selective cation channels, were critically involved in smooth muscle cell migration, proliferation, remodeling and contraction via regulating intracellular Ca2+ hemostasis. Here, we aim to evaluate the role of TRPV4 mediated epithelial dysfunction in HDM induced asthma by addressing these important issues: a, the effect of HDM treatment to the expression and function of epithelial TRPV4 channel, confirming the significance of TRPV4-derived Ca2+ influx in HDM-elevated epithelial [Ca2+]i; b, the contribution of TRPV4 to HDM caused alterations of epithelial electric resistance, apical junction complex and airway inflammation in vitro; c, the in vivo involvement of TRPV4 in HDM triggered AHR, airway epithelial barrier dysfunction, airway inflammation as well as airway remodeling. Hence, this project would identify the pivotal role of TRPV4 in HDM induced asthma, which might shed new insights for the prevention and treatment of asthma.