Mucus hypersecretion by airway epithelium and plugging of the airways are primary reasons of mortality in asthma patients and major causes of asthma disease progression and exacerbation. MUC5AC protein is a major component of airway mucus. MicroRNAs (miRNAs), a class of small noncoding RNAs, have emerged as moderators of MUC5AC production and secretion and are implicated in the pathogenesis of asthma. Recently, miR-330 has been reported to be downregulated in the blood of asthmatic patients, acting as a biomarker for asthma. The role of miR-330 in asthma, however, is unclear. Here, we showed that interleukin (IL)-13 induced MUC5AC secretion and inhibited miR-330 expression in a concentration-dependent manner in human bronchial epithelial cells (HBE16). Upregulation of miR-330 in HBE16 cells inhibited IL-13-induced MUC5AC secretion while, conversely, depletion of endogenous miR-330 exacerbated MUC5AC secretion. Munc18b (Syntaxin-Binding Protein 2; STXBP2) is a limiting component of the exocytic machinery of airway epithelial cells. We identified and validated that Munc18b was a direct target of miR-330 and miR-330 regulated MUC5AC secretion in HBE16 cells by acting directly on the 3'UTR of Munc18b mRNA. Collectively, these data reveal that miR-330 inhibits IL-13-induced MUC5AC secretion in human bronchial epithelial cells by targeting Munc18b, encouraging us to further explore the potential of manipulating miR-330 in treatment of airway diseases with mucus hypersecretion.
Keywords: Asthma; MUC5AC; Munc18b; miR-330.
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