Abstract
Backgroud: The chromatin remodeling factor Brg1 (Brahma-related gene 1) is an important nuclear protein that promotes the transcriptional activation or inhibition of target genes by regulating ATP hydrolysis to generate energy which rearranges the position of nucleosomes and the interaction of histone DNA. In this study, we explored the effect of Brg1 on airway mucus hypersecretion in asthma.Methods: Six-to-eight-week-old female wild-type C57BL/6 mice (wild-type, WT) and type II alveolar epithelial cells (AECIIs) specifically knockout Brg1 mice (Brg1fl/fl) were selected as the experimental subjects. The asthma group was established with house dust mite (HDM), and the control group was treated with normal saline (n=10). Wright's staining was used to detect inflammatory cells in bronchoalveolar lavage fluid (BALF). Invasive lung function was used to assess the airway compliance. Hematoxylin and eosin and periodic acid-schiff staining were used to detect mucus secretion. The virus was used to knock down the Brg1 gene in the bronchial epithelial cell line (16HBE) and stimulated with HDM. Immunohistochemistry was used to measure mucin glycoprotein 5AC (MUC5AC) protein expression in the airway epithelium and 16HBE cells. Western blotting was used to detect the expression of the MUC5AC and JAK1/2-STAT6 signaling pathways in mouse lung tissue and 16HBE. Co-immunoprecipitation (Co-IP) and Chromatin Immunoprecipitation (CHIP) were used to detect whether Brg1 could regulate the JAK1/2-STAT6 signaling pathway.Results: Specifically, knocking out the Brg1 gene in AECIIs can reduce airway inflammation, airway compliance, and mucus hypersecretion in asthma. Knockdown of the Brg1 gene can simultaneously reduce Interleukin-13 (IL-13) and the expression of MUC5AC protein in airway epithelial cells and the activation of the JAK1/2-STAT6 signaling pathway. The results of Co-IP and CHIP showed that Brg1 could bind to the JAK1/2 promoter region, regulating the activity of the JAK1/2-STAT6 pathway affects airway mucus secretion in asthma.Conclusion: Brg1 gene knockout in airway epithelial cells can reduce asthmatic airway mucus hypersecretion and the expression of MUC5AC protein in airway epithelial cells partly by inhibiting the activation of the JAK1/2-STAT6 signaling pathway.
miRNA‐34b/c regulates mucus secretion in RSV‐infected airway epithelial cells by targeting FGFR1
