Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells.
An Wang, Qiuyang Zhang, Yongmei Wang, Xue Li, Kuan Li, Yu Li, Jianhai Wang, Li Li, Huaiyong Chen
Author Information
An Wang: Department of Basic Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin 300350, P.R. China.
Qiuyang Zhang: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, P.R. China.
Yongmei Wang: Department of Pathology, Tianjin University Haihe Hospital, Tianjin 300350, P.R. China.
Xue Li: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, P.R. China.
Kuan Li: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, P.R. China.
Yu Li: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, P.R. China.
Jianhai Wang: Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin 300350, P.R. China.
Li Li: Department of Respiratory Medicine, Tianjin University Haihe Hospital, Tianjin 300350, P.R. China.
Huaiyong Chen: Department of Basic Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin 300350, P.R. China.
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.
