413 604

Cited 17 times in

Hypoxia-mediated mechanism of MUC5AC production in human nasal epithelial and its implication in rhinosinusitis

DC FieldValueLanguage
dc.contributor.author김창훈-
dc.contributor.author송현아-
dc.contributor.author윤주헌-
dc.contributor.author조형주-
dc.date.accessioned2015-01-06T16:46:49Z-
dc.date.available2015-01-06T16:46:49Z-
dc.date.issued2014-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/98754-
dc.description.abstractBACKGROUND: Excessive mucus production is typical in various upper airway diseases. In sinusitis, the expression of MUC5AC, a major respiratory mucin gene, increases. However, the mechanisms leading to mucus hypersecretion in sinusitis have not been characterized. Hypoxia due to occlusion of the sinus ostium is one of the major pathologic mechanisms of sinusitis, but there have been no reports regarding the mechanism of hypoxia-induced mucus hypersecretion. METHODS AND FINDINGS: This study aims to identify whether hypoxia may induce mucus hypersecretion and elucidate its mechanism. Normal human nasal epithelial (NHNE) cells and human lung mucoepidermoid carcinoma cell line (NCI-H292) were used. Sinus mucosa from patients was also tested. Anoxic condition was in an anaerobic chamber with a 95% N2/5% CO2 atmosphere. The regulatory mechanism of MUC5AC by anoxia was investigated using RT-PCR, real-time PCR, western blot, ChIP, electrophoretic mobility shift, and luciferase assay. We show that levels of MUC5AC mRNA and the corresponding secreted protein increase in anoxic cultured NHNE cells. The major transcription factor for hypoxia-related signaling, HIF-1α, is induced during hypoxia, and transfection of a mammalian expression vector encoding HIF-1α results in increased MUC5AC mRNA levels under normoxic conditions. Moreover, hypoxia-induced expression of MUC5AC mRNA is down-regulated by transfected HIF-1α siRNA. We found increased MUC5AC promoter activity under anoxic conditions, as indicated by a luciferase reporter assay, and mutation of the putative hypoxia-response element in MUC5AC promoter attenuated this activity. Binding of over-expressed HIF-1α to the hypoxia-response element in the MUC5AC promoter was confirmed. In human sinusitis mucosa, which is supposed to be hypoxic, expression of MUC5AC and HIF-1α is higher than in control mucosa. CONCLUSION: The results indicate that anoxia up-regulates MUC5AC by the HIF-1α signaling pathway in human nasal epithelia and suggest that hypoxia might be a pathogenic mechanism of mucus hypersecretion in sinusitis.-
dc.description.statementOfResponsibilityopen-
dc.format.extente98136-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHChromatin Immunoprecipitation-
dc.subject.MESHElectrophoretic Mobility Shift Assay-
dc.subject.MESHHumans-
dc.subject.MESHHypoxia/etiology-
dc.subject.MESHHypoxia/metabolism*-
dc.subject.MESHHypoxia-Inducible Factor 1, alpha Subunit/metabolism-
dc.subject.MESHLuciferases-
dc.subject.MESHMucin 5AC/metabolism*-
dc.subject.MESHMucus/secretion*-
dc.subject.MESHNasal Mucosa/secretion*-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHSignal Transduction/genetics-
dc.subject.MESHSignal Transduction/physiology*-
dc.subject.MESHSinusitis/complications-
dc.subject.MESHSinusitis/metabolism*-
dc.titleHypoxia-mediated mechanism of MUC5AC production in human nasal epithelial and its implication in rhinosinusitis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentMedical Research Center (임상의학연구센터)-
dc.contributor.googleauthorYoon-Ju Kim-
dc.contributor.googleauthorHyung-Ju Cho-
dc.contributor.googleauthorWoo-Chul Shin-
dc.contributor.googleauthorHyun-Ah Song-
dc.contributor.googleauthorJoo-Heon Yoon-
dc.contributor.googleauthorChang-Hoon Kim-
dc.identifier.doi10.1371/journal.pone.0098136-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01050-
dc.contributor.localIdA02076-
dc.contributor.localIdA02604-
dc.contributor.localIdA03936-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid24840724-
dc.contributor.alternativeNameKim, Chang Hoon-
dc.contributor.alternativeNameSong, Hyun Ah-
dc.contributor.alternativeNameYoon, Joo Heon-
dc.contributor.alternativeNameCho, Hyung Ju-
dc.contributor.affiliatedAuthorKim, Chang Hoon-
dc.contributor.affiliatedAuthorSong, Hyun Ah-
dc.contributor.affiliatedAuthorYoon, Joo Heon-
dc.contributor.affiliatedAuthorCho, Hyung Ju-
dc.citation.volume9-
dc.citation.number5-
dc.citation.startPagee98136-
dc.identifier.bibliographicCitationPLOS ONE, Vol.9(5) : e98136, 2014-
dc.identifier.rimsid38584-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.