Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells.
Gabrp
airway progenitor cells
asthma
differentiation
goblet cells
proliferation
Journal
Experimental and therapeutic medicine
ISSN: 1792-0981
Titre abrégé: Exp Ther Med
Pays: Greece
ID NLM: 101531947
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
04
09
2020
accepted:
12
03
2021
entrez:
19
5
2021
pubmed:
20
5
2021
medline:
20
5
2021
Statut:
ppublish
Résumé
Bronchial asthma is an intractable pulmonary disease that affects millions of individuals worldwide, with the overproduction of mucus contributing to high morbidity and mortality. Gamma-aminobutyric acid (GABA) is associated with goblet cell hyperplasia in the lungs of primate models and Club cells serve as airway epithelial progenitor cells that may differentiate into goblet and ciliated cells. In the present study, it was investigated whether the GABAA receptor pi (Gabrp) is essential for Club cell proliferation and differentiation in mice. Validation of microarray analysis results by reverse transcription-quantitative PCR (RT-qPCR) demonstrated that Gabrp is highly expressed in mouse Club cells. Predominant expression of Gabrp in mouse Club cells was further confirmed based on naphthalene-induced Club cell injury in mice, with organoid cultures indicating significant reductions in the organoid-forming ability of mouse Club cells in the presence of Gabrp antagonist bicuculline methiodide (BMI). Furthermore, the RT-qPCR results indicated that the mRNA levels of chloride channel accessory 3, pseudogene (Clca3p), mucin (Muc)5Ac and Muc5B were significantly decreased in BMI organoid cultures. These results suggested that blocking GABA signaling through Gabrp inhibits mouse Club cell proliferation, as well as differentiation into goblet cells. Therefore, targeting GABA/Gabrp signaling may represent a promising strategy for treating goblet cell hyperplasia in bronchial asthma.
Identifiants
pubmed: 34007329
doi: 10.3892/etm.2021.10152
pii: ETM-0-0-10152
pmc: PMC8120639
doi:
Types de publication
Journal Article
Langues
eng
Pagination
720Informations de copyright
Copyright: © Wang et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
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