南方医科大学学报2018,Vol.38Issue(1):42-47,6.
Brg1通过STAT6促进哮喘气道黏液高分泌
Brahma-related gene 1 promotes airway mucus hypersecretion via STAT6 in asthmatic mice
摘要
Abstract
Objective To investigate the effect of Brahma-related gene 1 (Brg1) on mucus hypersecretion in the airway of asthmatic mice and explore the mechanism. Methods Female 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. Results Compared 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). Conclusion Brg1 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.关键词
哮喘/Brg1/MUC5AC/STAT6/黏液高分泌Key words
asthma/Brahma-related gene 1/MUC5AC/STAT6/airway mucus hypersecretion引用本文复制引用
蔡霜,邹文静,王婷,王亚苹,丁凤霞,田代印,牛超,邹琳,符州..Brg1通过STAT6促进哮喘气道黏液高分泌[J].南方医科大学学报,2018,38(1):42-47,6.基金项目
国家自然科学基金(81670018) (81670018)
国家自然科学基金青年科学基金(81600022) Supported by National Natural Science Foundation of China (81670018). (81600022)