Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation

The Brg1 (Brahma-related gene 1) is an important chromatin remodeling factor protein. The Brg1 protein can promote the transcriptional activation or inhibit target genes through regulating ATP hydrolysis which rearranges the nucleosomes position and the histone DNA interaction. In this study, we explored the role of Brg1 in house dust mite (HDM) stimulated airway inflammation.

The wild-type C57BL/6 mice (wild-type, WT) and alveolar epithelial cells specifically knockout Brg1 mice (Brg1^fl/fl) were selected as the experimental subjects. HDM was used to stimulate human bronchial epithelial cells (16HBE) to construct an model of airway inflammation in vitro. The asthma group was established with HDM, and the control group was treated with normal saline. Wright's staining for the detection of differential counts of inflammatory cells in bronchoalveolar lavage fluid (BALF). Invasive lung function was used to assess the airway compliance. Hematoxylin and eosin (HE) staining and periodic acid-schiff (PAS) staining were used to detect mucus secretion. Immunohistochemistry was used to measure mucin glycoprotein 5AC (MUC5AC) protein expression in airway epithelium. Western blotting was used to detect the MUC5AC and JAK1/2-STAT6 proteins in mouse lung tissues and 16HBE cells. Co-immunoprecipitation (Co-IP) and Chromatin Immunoprecipitation (CHIP) were used to detect whether Brg1 could regulate the JAK1/2-STAT6 signaling pathway.

The airway inflammation, pulmonary ventilation resistance, airway mucus secretion, MUC5AC and IL-13 in BALF and MUC5AC protein expression in lung tissue of Brg1 knockout mice stimulated by HDM were lower than those of wild-type mice. The expression of MUC5AC protein in HDM stimulated Brg1 knockdown 16HBE cells was significantly lower than that in the control group. In vivo and in vitro, it was found that the activation of JAK1/2-STAT6 signal pathway in mouse lung tissue or 16HBE cells was inhibited after knockdown of Brg1 gene. The Co-IP and CHIP results showed that Brg1 could bind to the JAK1/2 promoter region and regulate the expression of JAK1/2 gene.

The Brg1 may promote the secretion of airway mucus stimulated by HDM through regulating the JAK1/2-STAT6 pathway. Knockdown of Brg1 reduced mucus secretion in HDM stimulated airway inflammation.