黏液过度生成是上下气道炎症性疾病的一个重要特征，不仅导致黏液纤毛清除功能紊乱，影响炎症进程及转归，甚至堵塞气道危及生命，同时也引起患者严重的精神心理反应。黏蛋白合成和分泌增加是导致黏液过度生成的主要原因。黏蛋白调节包括转录、跨膜分泌和黏液细胞增殖三个方面，其中转录和黏液细胞增殖分别从细胞和组织水平影响黏蛋白合成。TMEM16A作为钙激活氯离子通道的典型代表，可以调节黏蛋白跨膜分泌，但其对黏蛋白转录及黏液细胞增殖的调节作用未见报道。本课题组前期研究提示TMEM16A可能从转录及黏液细胞增殖两个途径调节鼻黏膜上皮黏蛋白MUC5AC的合成，其详尽机制有待阐明。因此，本课题拟采用鼻黏膜上皮炎症模型，通过细胞电生理、分子生物学及免疫学手段，从转录水平和黏液细胞增殖角度研究TMEM16A对黏蛋白MUC5AC合成的调控机制，有望从干预黏蛋白合成的源头发现新的干预靶点，治疗气道黏液异常相关疾病。

Mucus overproduction is one of the common features of upper and lower airway inflammatory diseases, such as chronic rhinosinusitis with or without nasal polyps, allergic rhinitis, asthma and chronic obstructive pulmanary diseases, and so on. .Excess mucus is likely due to increased biosynthesis and secretion of the secretory mucins. Transmembrane protein with unknown function 16A (TMEM16A) found recently is the only ion channel summarizes endogenous calcium-activated chloride channels (CaCCs) properties. TMEM16A has been demonstrated to regulate mucin secretion, but whether it regulates mucin production through transcription and mucous cells proliferation needs to be clarified. From our previous study, TMEM16A may also play potential important roles in the regulation of MUC5AC transcription and mucous cells proliferation. Ussing chamber techniques combined with molecular biology and immunological methods, we aim to reveal TMEM16A regulatory mechanisms on MUC5AC production from transcription and mucous cell proliferation in nasal epithelium, which will provide a theoretical basis to improve abnormal mucus secretion in inflammatory diseases of upper and lower airways.