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, Zhou Fu

Research output: Contribution to journalArticlepeer-review

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). CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)42-47
Number of pages6
JournalNan fang yi ke da xue xue bao = Journal of Southern Medical University
Volume38
Issue number1
DOIs
StatePublished - Jan 30 2018
Externally publishedYes

Keywords

  • Brahma-related gene 1
  • MUC5AC
  • STAT6
  • airway mucus hypersecretion
  • asthma

ASJC Scopus subject areas

  • Medicine(all)

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