Brahma-related gene 1 promotes airway mucus hypersecretion via STAT6 in asthmatic mice
10.3969/j.issn.1673-4254.2018.01.007
- VernacularTitle:Brg1通过STAT6促进哮喘气道黏液高分泌
- Author:
Shuang CAI
1
;
Wenjing ZOU
;
Ting WANG
;
Yaping WANG
;
Fengxia DING
;
Daiyin TIAN
;
Chao NIU
;
Lin ZOU
;
Zhou FU
Author Information
1. 重庆医科大学附属儿童医院儿科研究所//儿童发育疾病研究教育部重点实验室//儿童发育重大疾病国家国际科技合作基地//儿科学重庆市重点实验室
- Keywords:
asthma;
Brahma-related gene 1;
MUC5AC;
STAT6;
airway mucus hypersecretion
- From:
Journal of Southern Medical University
2018;38(1):42-47
- CountryChina
- Language:Chinese
-
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.
