• Nan Fang Yi Ke Da Xue Xue Bao · Jan 2018

    [Brahma-related gene 1 promotes airway mucus hypersecretion via STAT6 in asthmatic mice].

    • Shuang Cai, Wenjing Zou, Ting Wang, Yaping Wang, Fengxia Ding, Daiyin Tian, Chao Niu, Lin Zou, and Zhou Fu.
    • Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
    • Nan Fang Yi Ke Da Xue Xue Bao. 2018 Jan 30; 38 (1): 42-47.

    ObjectiveTo investigate the effect of Brahma-related gene 1 (Brg1) on mucus hypersecretion in the airway of asthmatic mice and explore the mechanism.MethodsFemale C57bl/6 mice aged 6-8 weeks were randomized into wild-type control group, wild-type asthma group, Brg1-/- group with Brg1 gene knockdown in type Ⅱ alveolar epithelial cells, and Brg1-/-+ asthma group (n=10). The mice in asthma group and Brg1-/-+asthma group were sensitized with ovalbumin (OVA) to establish asthmatic models. PAS staining was used to determine the number of goblet cells and mucus secretion in the airway. Real-time PCR was used to detect the expression of MUC5AC mRNA in the lung tissues. The levels of mucin MUC5AC and interleukin-13 (IL-13) in the bronchoalveolar lavage fluid (BALF) were detected with ELISA and immunohistochemistry, and the expressions of STAT6 and p-STAT6 in the lung tissue were detected using Western blotting.ResultsCompared with the control mice, wild-type asthmatic mice showed obvious mucus hypersecretion and increased MUC5AC mRNA in the airway with significantly increased IL-13 and MUC5AC levels in the BALF and activation of p-STAT6 in the lung tissues (P < 0.05). In the transgenic mice with Brg1 gene knockdown, airway mucus secretion and MUC5AC mRNA expression was significantly reduced following OVA challenge compared with those in the wild-type asthmatic mice; IL-13 and MUC5AC levels in the BALF and p-STAT6 expression in the lung tissues were also significantly decreased in the transgenic mice (P < 0.05).ConclusionsBrg1 gene knockdown in type Ⅱ alveolar epithelial cells alleviates OVA-induced airway mucus hypersecretion and reduces the expression of MUC5AC in C57bl/6 mice possibly by inhibiting STAT6 activation, suggesting the role of Brg1 in promoting asthmatic airway mucus hypersecretion.

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