목적: Repetitive injury or damage to the airway epithelium leads to airway remodeling including ciliated cell loss and mucous cell hyperplasia, causing abnormal mucociliary clearance and pathogen colonization. Proteolytic maturation of many growth and differentiation factors involved in tissue remodeling is controlled by proprotein convertases (PCs). During repair of airway injury, Notch signaling regulates the differentiation of airway basal cells (BCs), primarily towards secretory lineages. Endoproteolytic maturation of Notch1, a specific Notch receptor, is mediated by the furin-like PCs, but the role of PCs in Notch1-mediated cell fate decisions in the airway epithelium is largely unknown. 방법:In this study, we investigated whether decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, regulates the Notch1-dependent differentiation of airway BCs by using an air-liquid interface (ALI) culture model of human nasal epithelial cells (HNECs). 결과:We observed that CMK increases expression of ciliated cell markers FOXJ1 and Tektin, and has no effect on the ciliary beat frequency in HNECs. SEM and TEM images obtained at ALI day 14 in CMK-treated cultures revealed an increase in the number of ciliated cells. Comparative microarray analysis also showed that CMK induced expression of cilia-related genes in HNECs. CMK inhibited Notch1 processing and expression of Notch1 downstream target genes (eg., HEY1, ID1, ID3). Furthermore, specific lentiviral shRNA-mediated furin knockdown significantly reduced Notch1 processing. ZnSO4-induced ciliary removal on mouse nasal respiratory epithelium was recovered faster in CMK-treated than in control mice. 결론:Our data strongly suggest that the secretory lineage specification and differentiation of BCs is dependent on Notch1 processing mediated by furin, suggesting the possibility of using PC inhibitor in airway mucous hyperplasia.