气道上皮屏障损伤是哮喘启动的关键环节，上皮来源的外泌体参与介导哮喘气道炎症，但其对气道上皮屏障功能的影响目前尚不明确。我们研究显示，PTEN/PI3K/VEGF途径参与哮喘致敏物HDM所致的气道上皮屏障损伤。HDM刺激气道上皮外泌体释放，这些外泌体可降低气道上皮细胞PTEN表达，上调VEGF并破坏屏障功能。且外泌体miR-21在HDM刺激的气道上皮细胞富集，miR-21可抑制PTEN mRNA表达。提示外泌体介导气道上皮屏障损伤，机制与其内容物miR-21调控PTEN/PI3K/VEGF轴相关。本项目拟利用超速离心技术提取哮喘模型上皮源性外泌体，探讨其对上皮屏障功能及通路蛋白PTEN、PI3K和VEGF的影响。同时拮抗miR-21，在体内外研究外泌体miR-21经PTEN/PI3K/VEGF轴调控哮喘气道上皮屏障损伤的机制，为寻找哮喘气道上皮屏障受损的新靶点，完善哮喘发病机制提供理论基础。

The airway epithelial barrier plays a crucial role in activation of asthma airway inflammation. Airway epithelium-derived exosomes involved in mediating asthmatic airway inflammation, but its effect on airway epithelial barrier function is unclear. In our previous study, we’ve demonstrated that common allergens house dust mite(HDM) can disrupt airway barrier by PTEN/PI3K/VEGF pathway. Further, human bronchial epithelial cells (HBECs) exposed to HDM significantly increase the release of exosomes.These exosomes increased FITC-dextran permeability of epithelial layer,down-regulated PTEN and increased VEGF expression. Exosomal miRNA microarray analysis revealed that miR-21 increased in HDM-induced HBEC-derived exosomes.Luciferase report showed miR-21 inhibit PTEN expression.This indicates that exosomes can damage airway epithelial barrier function, and its mechanism may be related to its content miR-21 regulation of PTEN/PI3K/VEGF axis.. This study will isolate airway epithelium-derived exosomes from asthma model by using ultrafiltration centrifugalization. Then we investigate the effects of exosomes derived from HDM–treated on epithelial barrier function and pathway protein PTEN，PI3K/Akt and VEGF expression. Meanwhile we use miR-21 mimics and miR-21 inhibitors to deep explore the role and the possible mechanism of exosomal miR-21 on asthmatic airway epithelial barrier dysfunction via PTEN/PI3K/VEGF pathway both in vitro and in vivo. The project aims to find new targets for therapeutic intervention in airway epithelial injury and provide new insights in the pathogenesis of asthma.