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Cell-Type-Specific Expression of Hyaluronan Synthases HAS2 and HAS3 Promotes Goblet Cell Hyperplasia in Allergic Airway Inflammation

DC Field Value Language
dc.contributor.author윤주헌-
dc.contributor.author조형주-
dc.contributor.author이상남-
dc.date.accessioned2022-12-22T03:45:17Z-
dc.date.available2022-12-22T03:45:17Z-
dc.date.issued2022-09-
dc.identifier.issn1044-1549-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/191973-
dc.description.abstractAllergic rhinitis (AR) is a multifactorial airway disease characterized by basal and goblet cell hyperplasia. Hyaluronic acid (HA) is a major component of extracellular matrix and a critical contributor to tissue repair and remodeling after injury. We previously demonstrated that the intermediate progenitor cell (IPC) surface marker CD44v3 is upregulated in the basal and suprabasal layers of well-differentiated primary human nasal epithelial (HNE) cells after stimulation with the Th2 (T-helper cell type 2) cytokine IL-4, and an antibody blocking the CD44v3-HA interaction suppressed IL-4-induced goblet cell hyperplasia. We now show that the expression of HA and two HA synthases, HAS2 and HAS3, was upregulated in both the nasal surface epithelium of subjects with AR and IL-4-stimulated HNE cells. Inhibition of HA synthesis by 4-methylumbelliferone suppressed IL-4-induced goblet cell hyperplasia. Moreover, HAS2 and HAS3 were expressed in IPCs depending on the differentiation events, as follows: the rapid, transient upregulation of HAS2 induced basal IPC proliferation and basal-to-suprabasal transition, whereas the delayed upregulation of HAS3 promoted the transition of suprabasal IPCs to a goblet cell fate. 4-methylumbelliferone treatment in a house dust mite-induced murine AR model attenuated goblet cell metaplasia. Last, HA concentrations in nasal epithelial lining fluids from patients with AR positively correlated with the concentrations of mediators causing allergic inflammation. These data suggest that HA produced after the sequential upregulation of HAS2 and HAS3 contributes to goblet cell hyperplasia in allergic airway inflammation and modulates disease progression.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAmerican Thoracic Society-
dc.relation.isPartOfAMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHGoblet Cells* / drug effects-
dc.subject.MESHGoblet Cells* / enzymology-
dc.subject.MESHGoblet Cells* / pathology-
dc.subject.MESHHumans-
dc.subject.MESHHyaluronan Synthases* / metabolism-
dc.subject.MESHHyaluronic Acid / metabolism-
dc.subject.MESHHymecromone / pharmacology-
dc.subject.MESHHymecromone / therapeutic use-
dc.subject.MESHHyperplasia / genetics-
dc.subject.MESHHyperplasia / pathology-
dc.subject.MESHInterleukin-4 / metabolism-
dc.subject.MESHMice-
dc.subject.MESHRhinitis, Allergic* / drug therapy-
dc.subject.MESHRhinitis, Allergic* / enzymology-
dc.subject.MESHRhinitis, Allergic* / pathology-
dc.titleCell-Type-Specific Expression of Hyaluronan Synthases HAS2 and HAS3 Promotes Goblet Cell Hyperplasia in Allergic Airway Inflammation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Otorhinolaryngology (이비인후과학교실)-
dc.contributor.googleauthorSang-Nam Lee-
dc.contributor.googleauthorSeol Ah Yoon-
dc.contributor.googleauthorJi Min Song-
dc.contributor.googleauthorHyung Chul Kim-
dc.contributor.googleauthorHyung-Ju Cho-
dc.contributor.googleauthorAugustine M K Choi-
dc.contributor.googleauthorJoo-Heon Yoon-
dc.identifier.doi10.1165/rcmb.2021-0527oc-
dc.contributor.localIdA02604-
dc.contributor.localIdA03936-
dc.relation.journalcodeJ00113-
dc.identifier.eissn1535-4989-
dc.identifier.pmid35679095-
dc.identifier.urlhttps://www.atsjournals.org/doi/10.1165/rcmb.2021-0527OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed-
dc.subject.keywordallergic rhinitis-
dc.subject.keywordgoblet cell hyperplasia-
dc.subject.keywordhuman nasal epithelial cells-
dc.subject.keywordhyaluronic acid-
dc.subject.keywordinterleukin-4-
dc.contributor.alternativeNameYoon, Joo Heon-
dc.contributor.affiliatedAuthor윤주헌-
dc.contributor.affiliatedAuthor조형주-
dc.citation.volume67-
dc.citation.number3-
dc.citation.startPage360-
dc.citation.endPage374-
dc.identifier.bibliographicCitationAMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.67(3) : 360-374, 2022-09-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers

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