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Overexpressed proprotein convertase 1/3 induces an epithelial-mesenchymal transition in airway epithelium

Authors
 Sang-Nam Lee  ;  Da-Hyung Lee  ;  Myung Hyun Sohn  ;  Joo-Heon Yoon 
Citation
 EUROPEAN RESPIRATORY JOURNAL, Vol.42(5) : 1379-1390, 2013 
Journal Title
 EUROPEAN RESPIRATORY JOURNAL 
ISSN
 0903-1936 
Issue Date
2013
MeSH
Animals ; Cell Line ; Epithelial Cells/cytology* ; Epithelial-Mesenchymal Transition* ; Epithelium/metabolism* ; Gene Expression Profiling ; Gene Expression Regulation* ; Goblet Cells/metabolism ; Humans ; Inflammation ; Mice ; Nasal Mucosa/metabolism ; Nasal Polyps/metabolism* ; Neuroendocrine Cells/cytology ; Phenotype ; Proprotein Convertase 1/physiology* ; Respiratory System/cytology ; Sinusitis/metabolism ; Wound Healing
Keywords
Animals ; Cell Line ; Epithelial Cells/cytology* ; Epithelial-Mesenchymal Transition* ; Epithelium/metabolism* ; Gene Expression Profiling ; Gene Expression Regulation* ; Goblet Cells/metabolism ; Humans ; Inflammation ; Mice ; Nasal Mucosa/metabolism ; Nasal Polyps/metabolism* ; Neuroendocrine Cells/cytology ; Phenotype ; Proprotein Convertase 1/physiology* ; Respiratory System/cytology ; Sinusitis/metabolism ; Wound Healing
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.
Full Text
http://erj.ersjournals.com/content/42/5/1379.long
DOI
10.1183/09031936.00100412
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Yoon, Joo Heon(윤주헌)
Lee, Da Hyung(이다형)
Lee, Sang Nam(이상남)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88333
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