E钙粘蛋白（E-cadherin）作为气道上皮耐受和促炎表型平衡的分子开关，参与调节哮喘气道炎症及屏障功能。我们已经证明活性维生素D（1,25(OH)2D3）可以保护气道上皮屏障，并抑制致敏原屋尘螨（HDM）、甲苯二异氰酸酯（TDI）引起的E-cadherin破坏和ERK磷酸化。也发现活性维生素D可以显著上调TSLP表达，那么TSLP是否介导了活性维生素D的屏障保护作用？进一步预实验显示，低浓度TSLP即可保护正常气道上皮屏障功能，也可显著减少HDM致气道上皮屏障损伤和E-cadherin的破坏。本项目拟采用小鼠气道VDR基因敲除、siRNA等方法，从体内外阐明活性维生素D通过VDR-TSLP-ERK途径对哮喘气道上皮"耐受性上皮表型"E-cadherin的影响及可能的分子机制，为确立维生素D作为哮喘防治新靶标提供科学依据。

E-cadherin has been considered as a molecular switch to regulate the balance between airway epithelium tolerance and proinflammatory phenotype ,involving in regulating airway inflammation. We have demonstrated that the active vitamin D（1,25(OH)2D3）could significantly improve the airway epithelial barrier functionas well as inhibit the abnormal expression and distribution of the E-cadherin and extracellular signal-regulated kinase (ERK) phosphorylation caused by house dust mites (HDM) and toluene diisocyanate (TDI). Moreover,we also found that 1,25(OH)2D3 could dramaticlly increase TSLP expression. However, whether the protective effect of 1,25(OH)2D3 on epitheim functions is due to the upregulation of TSLP remains unresolved? To address these critical issues, our preliminary datas howed that, low concentrations of TSLP could enhancethe normal epithelial barrier function.Also, TSLP reduced HDM-induced airway epithelial barrier injury and markedly increased the expression of E-cadherin. This project is intended to investigate the barrier protective effects of 1,25(OH)2D3, focusing on vitamin D receptor（VDR）-TSLP-ERK pathway by using airway VDR knock-out mice,siRNA and other methods, which may provide new insights on therapy with vitamin D for prevention and treatment of asthma and targetting the key molecule of tolerogenic epithelial phenotype E-cadherin.