Brg1 aggravates airway inflammation in asthma via inhibition of the PI3K/Akt/mTOR pathway

The PI3K/Akt/mTOR pathway is thought to be closely associated with airway inflammation and is regulated by various upstream proteins. Brahma-related gene 1 (Brg1) plays an important role in chromatin remodeling and facilitates recruitment of essential transcription factors, leading to regulation of gene expression. Thus, the present study aimed at evaluating the anti-inflammatory role of Brgl1 on house dust mite (HDM)-induced asthma through regulating the PI3K/Akt/mTOR pathway. The Brg(fl/fl) mice were crossbred with the SFTPC-Cre mice to generate bronchial epithelial cell specific Brg1 knockout mice, and LY294002 was used to inhibit PI3K. Western blot, immunofluorescence, immunoprecipitation, and immunohistochemical staining were used to detect the expression of proteins. An increase in Brg1 and a decrease in the PI3K/Akt/mTOR pathway activity were detected in asthmatic mice, but not in control mice. When Brg1 was knocked out, the asthma severity was ameliorated and the PI3K/Akt/mTOR pathway was activated. However, this protective effect could be suppressed by LY294002. Additionally, we observed that Brgl was co-localized and co-immunoprecipitated with PI3K, using immunofluorescence and immunoprecipitation assays. Our results suggest that Brgl might play an essential role in maintaining airway inflammation and affect the PI3K/Akt/mTOR pathway in asthma. (C) 2018 Elsevier Inc. All rights reserved.