Mucus hypersecretion and goblet cell upregulation are common features of chronic rhinosinusitis with nasal polyps (CRSwNP). Although epidermal growth factor (EGF) has been reported to stimulate the expression of MUC5AC, the major macro-molecular constituent of airway mucus, the precise mechanisms underlying the regulation of MUC5AC expression are still not fully understood. The aim of this study therefore was to investigate the role of EGF in regulation of mucin MUC5AC expression and define the involvement of transmembrane protein 16A (TMEM16A) in mediating the EGF-induced mucus overexpression. Human nasal epithelial cells (HNECs) derived from tissue of patients with CRSwNP and control subjects were established as air–liquid interface (ALI) cultures. Differentiated cultures were treated with different concentrations of EGF for 4–24 h, and assessed for the expression of TMEM16A and MUC5AC by real-time RT-PCR, Western blotting, ELISA and immunofluorescence. Cultures pretreated for 30 min with T16Ainh-A01 (a specific TMEM16A inhibitor) or LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) were also assessed similarly following EGF treatment. EGF treatment (10–100 ng/ml for 4–24 h) significantly increased the expression of both TMEM16A and MUC5AC mRNA and protein, as well as the percentage of TMEM16A-positive cells, MUC5AC-positive cells and cells coexpressing TMEM16A and MUC5AC in HNECs compared to control non-EGF-treated HNECs. Pretreatment of the HNECs with T16Ainh-A01 and LY294002 attenuated these EGF-induced effects. This study demonstrated that EGF upregulates the expression of MUC5AC in HNECs from CRSwNP patients. Furthermore, the EGF-mediated regulation of MUC5AC expression is likely to involve a PI3K-TMEM16A signalling pathway in CRSwNP.

中文翻译：

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在伴有鼻息肉的慢性鼻窦炎中，表皮生长因子通过 TMEM16A 上调 MUC5AC 的表达。

粘液分泌过多和杯状细胞上调是慢性鼻窦炎伴鼻息肉 (CRSwNP) 的常见特征。尽管据报道表皮生长因子 (EGF) 可刺激 MUC5AC（气道粘液的主要大分子成分）的表达，但调节 MUC5AC 表达的确切机制仍不完全清楚。因此，本研究的目的是研究 EGF 在调节粘蛋白 MUC5AC 表达中的作用，并确定跨膜蛋白 16A (TMEM16A) 在介导 EGF 诱导的粘液过度表达中的作用。来自 CRSwNP 患者和对照受试者组织的人鼻上皮细胞 (HNEC) 被确定为气液界面 (ALI) 培养物。分化的培养物用不同浓度的 EGF 处理 4-24 小时，并通过实时RT-PCR、Western印迹、ELISA和免疫荧光评估TMEM16A和MUC5AC的表达。用 T16Ainh-A01（一种特定的 TMEM16A 抑制剂）或 LY294002（一种磷酸肌醇 3-激酶 (PI3K) 抑制剂）预处理 30 分钟的培养物也在 EGF 处理后进行了类似的评估。EGF 处理（10-100 ng/ml，4-24 小时）显着增加了 TMEM16A 和 MUC5AC mRNA 和蛋白质的表达，以及 TMEM16A 阳性细胞、MUC5AC 阳性细胞和共表达 TMEM16A 和 MUC5AC 的细胞的百分比。 HNEC 与对照非 EGF 处理的 HNEC 相比。用 T16Ainh-A01 和 LY294002 预处理 HNEC 可减弱这些 EGF 诱导的作用。该研究表明，EGF 上调 CRSwNP 患者 HNEC 中 MUC5AC 的表达。此外，