Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells

xlomafota13 shared this article with you from Inoreader Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jul;22(1):720. doi: 10.3892/etm.2021.10152. Epub 2021 May 3. ABSTRACT 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. PMID:34007329 | PMC:PMC8120639 | DOI:10.3892/etm.2021.10152 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.