热休克蛋白90（HSP90）在哮喘气道炎症反应中具有重要作用，而致敏物对气道上皮屏障功能的破坏是启动哮喘气道炎症的关键步骤。E钙黏蛋白（E-cadherin）作为气道上皮耐受和促炎平衡的分子开关，扮演着气道上皮屏障“守护者”的角色。我们前期研究发现：屋尘螨（HDM）/甲苯二异氰酸酯（TDI）刺激气道上皮细胞可引起E-cadherin的表达和分布异常，进而增加上皮通透性，同时该致敏物可诱导上皮细胞HSP90α的表达和分泌增加，而利用抗HSP90α单抗预处理细胞，可改善E-cadherin的异常，从而降低气道上皮通透性。这提示致敏物可通过诱导上皮细胞分泌HSP90α，靶向E-cadherin引起气道上皮屏障功能破坏。本研究拟利用CRISPR-Cas9基因敲除技术，在细胞水平阐明分泌型HSP90α如何调控致敏物诱导气道上皮屏障功能破坏，为哮喘早期防治提供新靶点。

Heat shock protein 90 (HSP90) plays a critical role in airway inflammation of asthma, and the destruction of allergen on airway epithelial barrier can induce asthma airway inflammation.E-cadherin, a key molecule, regulates airway epithelium tolerance and pro-inflammation, acts a maintenance for airway barrier integrity.In our previous study, HDM or TDI can disrupt the expression and distribution of E-cadherin, then increase airway epithelial permeability. Meanwhile, they can increase the expression and secretion of Hsp90α. Intriguingly, pretreating epithelial cells with anti-Hsp90α mAb can protect E-cadherin and decrease airway epithelial permeability. These phenomenon indicates that Hsp90α is secreted by epithelium under allergens can induce airway epithelia barrier injury through targeting E-cadherin. This project will take advantage of CRISPR-Cas9 Gene knockout technology, to explain how does the secreted Hsp90α regulate the function of airway epithelia barrier induced by allergen in vitro, to provide a new target for early prevention and treatment of asthma.