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CD44v3-Positive Intermediate Progenitor Cells Contribute to Airway Goblet Cell Hyperplasia

Authors
 Sang-Nam Lee  ;  Su-Jin Kim  ;  Seol Ah Yoon  ;  Ji Min Song  ;  Ji-Suk Ahn  ;  Hyung Chul Kim  ;  Augustine M K Choi  ;  Joo-Heon Yoon 
Citation
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, Vol.64(2) : 247-259, 2021-02 
Journal Title
 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 
ISSN
 1044-1549 
Issue Date
2021-02
MeSH
Biomarkers / metabolism ; Cell Differentiation / physiology ; Cell Proliferation / physiology ; Cells, Cultured ; Epithelial Cells / metabolism ; Epithelial Cells / pathology ; Exons / genetics ; Goblet Cells / metabolism* ; Goblet Cells / pathology ; Humans ; Hyaluronan Receptors / metabolism* ; Hyperplasia / metabolism* ; Hyperplasia / pathology ; Hypersensitivity / metabolism ; Hypersensitivity / pathology ; Inflammation / metabolism ; Inflammation / pathology ; Mucins / metabolism ; Nasal Mucosa / metabolism ; Nasal Mucosa / pathology ; RNA, Messenger / genetics ; Respiratory System / metabolism* ; Respiratory System / pathology ; Stem Cells / metabolism* ; Stem Cells / pathology ; Up-Regulation / physiology
Keywords
CD44 ; allergic airway disease ; human nasal epithelial cells ; interleukin-4 ; intermediate progenitor cells
Abstract
In allergic airway diseases, intermediate progenitor cells (IPCs) increase in number in the surface epithelium. IPCs arise from basal cells, the origin of hallmark pathological changes, including goblet cell hyperplasia and mucus hypersecretion. Thus, targeting IPCs will benefit future treatment of allergic airway diseases. However, the lack of adequate cell surface markers for IPCs limits their identification and characterization. We now show that CD44 containing exon v3 (CD44v3) is a surface marker for IPCs that are capable of both proliferating and generating differentiated goblet cells in allergic human nasal epithelium. In primary human nasal epithelial cells that had differentiated at an air-liquid interface, IL-4 upregulated mRNA expression of three CD44v variants that include exon v3 (CD44v3-v6, CD44v3,v8-v10, and CD44v3-v10), and it induced expression of CD44v3 protein in the basal and suprabasal layers of the culture. FACS analysis revealed two subpopulations differing in CD44v3 concentrations, as follows: CD44v3low cells expressed high amounts of proliferative and basal cell markers (Ki-67 and TP63), whereas CD44v3high cells strongly expressed progenitor and immature and mature goblet cell markers (SOX2, CA2, and SPDEF). Importantly, a blocking anti-CD44 antibody suppressed IL-4-induced mucin production by human nasal epithelial cells. Furthermore, CD44v3 was coexpressed with TP63, KRT5, or SOX2 and was upregulated in the basal and suprabasal layers of the nasal surface epithelium of subjects with allergic rhinitis. Taken together, these data demonstrate that high CD44v3 expression contributes to goblet cell hyperplasia in inflammation of the allergic airway.
Full Text
https://www.atsjournals.org/doi/10.1165/rcmb.2020-0350OC
DOI
10.1165/rcmb.2020-0350OC
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
Lee, Sang Nam(이상남)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182158
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