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

Authors
 Sang-Nam Lee  ;  Seol Ah Yoon  ;  Ji Min Song  ;  Hyung Chul Kim  ;  Hyung-Ju Cho  ;  Augustine M K Choi  ;  Joo-Heon Yoon 
Citation
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.67(3) : 360-374, 2022-09 
Journal Title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
ISSN
 1044-1549 
Issue Date
2022-09
MeSH
Animals ; Goblet Cells* / drug effects ; Goblet Cells* / enzymology ; Goblet Cells* / pathology ; Humans ; Hyaluronan Synthases* / metabolism ; Hyaluronic Acid / metabolism ; Hymecromone / pharmacology ; Hymecromone / therapeutic use ; Hyperplasia / genetics ; Hyperplasia / pathology ; Interleukin-4 / metabolism ; Mice ; Rhinitis, Allergic* / drug therapy ; Rhinitis, Allergic* / enzymology ; Rhinitis, Allergic* / pathology
Keywords
allergic rhinitis ; goblet cell hyperplasia ; human nasal epithelial cells ; hyaluronic acid ; interleukin-4
Abstract
Allergic 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.
Full Text
https://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
DOI
10.1165/rcmb.2021-0527oc
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191973
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