title: Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium.
abstract: The proprotein convertases (PCs) are serine proteases responsible for the proteolytic maturation of many precursor proteins involved in upper airway remodelling during nasal polyposis. We have previously found that PC1/3 is expressed in human nasal mucosa. However, whether PC1/3 is related to nasal polyp formation has not been investigated. To gain insight into the functional role of PC1/3 in nasal polyps, we determined PC1/3 expression in nasal polyps by immunostaining, Western blotting and enzyme assays and generated stable cells expressing PC1/3 using airway epithelial cell line NCI-H292. Nasal polyps exhibit increased PC1/3 expression compared to normal nasal mucosa. PC1/3 was expressed in neuroendocrine cells in normal nasal mucosa and it was also expressed in goblet and ciliated cells in nasal polyps. NCI-H292 cells stably expressing PC1/3 displayed morphological changes, enhanced cell proliferation and migration, downregulation of E-cadherin and cytokeratins and upregulation of N-cadherin, vimentin, matrix metalloproteinase-2, collagen-I, snail and twist. Importantly, PC1/3 expression was positively correlated with epithelial-mesenchymal transition in cultured human nasal epithelial cells and in nasal polyps. Taken together, our data suggest that PC1/3 overexpression induces morphological and phenotypic epithelial-mesenchymal transition changes of airway epithelial cells and these changes may contribute to the pathogenesis of nasal polyps.
authors: Yonsei University College of Medicine, Seoul.
authors: Sang-Nam
authors: SN
authors: Lee
authors: Da-Hyung
authors: DH
authors: Lee
authors: Myung Hyun
authors: MH
authors: Sohn
authors: Joo-Heon
authors: JH
authors: Yoon
mesh_terms: D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology*; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D051379:Mice; D009297:Nasal Mucosa / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism*; D055099:Neuroendocrine Cells / Q000166:cytology; D010641:Phenotype; D045664:Proprotein Convertase 1 / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology; D012852:Sinusitis / Q000378:metabolism; D014945:Wound Healing
chemical_list: D045664:Proprotein Convertase 1