TY - JOUR T1 - Proprotein convertase 5/6A induces squamous differentiation of airway epithelial cells JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3882 AU - Sang-Nam Lee AU - Da-Hyung Lee AU - Joo-Heon Yoon Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3882.abstract N2 - Squamous metaplasia in airway epithelium is a pathological process arising from abnormal remodeling/repair responses to injury.Proteolytic maturation of many growth and differentiation factors involved in tissue remodelingis controlled by proprotein convertases (PCs). However, the role of these convertases in airway remodeling remains poorly understood. Using a retinoic acid deficiency-induced squamous metaplasia model of cultured human nasal epithelial cells (HNECs), we observed a significant increase in the expression of PC5/6A, a PC member, and bone morphogenetic protein-2 (BMP-2), a candidate substrate for PCs. Specific lentiviral shRNA-mediated PC5/6A knockdown and pharmacological inhibition of PC5/6A and BMP-2 activities suppressed squamous differentiation, promoted mucociliary differentiation, and down-regulated the BMP-2 signaling pathways. Surprisingly, under retinoic acid-sufficient culture conditions for mucociliary differentiation of HNECs, the addition of exogenous BMP-2 to epithelial cell cultures before the initiation of differentiation induced squamous differentiation. Furthermore, PC5/6A and BMP-2 were highly expressed in hyperproliferative and metaplastic squamous epitheliumof human nasal polyps. Taken together, PC5/6A is involved in squamous differentiation of HNECs, through up-regulation of the BMP-2 signaling pathway, pointing to a potential therapeutic target for the prevention of chronic airway diseases that exhibit squamous metaplasia. ER -