[1]蔡霜,邹文静,王婷,等.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,(01):42.
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Brg1通过STAT6促进哮喘气道黏液高分泌()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2018年01期
页码:
42
栏目:
出版日期:
2018-01-20

文章信息/Info

Title:
Brahma-related gene 1 promotes airway mucus hypersecretion via STAT6 in asthmatic mice
作者:
蔡霜邹文静王婷王亚苹丁凤霞田代印牛超邹琳符州
关键词:
哮喘Brg1MUC5ACSTAT6黏液高分泌
Keywords:
asthma Brahma-related gene 1 MUC5AC STAT6 airway mucus hypersecretion
摘要:
目的研究染色质重构复合物核心催化亚基(Brg1)对哮喘小鼠气道黏液高分泌的影响及其作用机制。方法将6~8周龄 雌性野生型C57bl/6小鼠和Brg1-/-小鼠(Ⅱ型肺泡上皮细胞AEC2s上特异性条件敲低Brg1的C57bl/6小鼠)随机分为4组:正常 对照组、哮喘组、Brg1敲低对照组(Brg1-/-)和Brg1敲低后构建哮喘模型组(Brg1-/-+哮喘),每组10只。哮喘组和Brg1-/-+哮喘组用 鸡卵清蛋白(OVA)制备过敏性哮喘模型,对照组用生理盐水代替。收取标本,用ELISA检测小鼠支气管肺泡灌洗液(BALF)中 黏蛋白MUC5AC和IL-13的表达。糖原染色检测小鼠气道杯状细胞的增生和黏液分泌,q-PCR和免疫组化检测各组小鼠气道 黏蛋白MUC5AC的表达和定量。Western blot检测各组小鼠肺组织中STAT6、p-STAT6的表达。结果Brg1-/-+哮喘组较哮喘组 气道杯状细胞增生和黏液分泌均显著减少,BALF中IL-13、MUC5AC表达明显降低,肺组织MUC5AC mRNA表达显著降低, 同时肺组织STAT6和磷酸化STAT6显著下调。结论Brg1-/-敲低的小鼠建立哮喘模型时气道黏液分泌较野生型小鼠减轻,其可 能通过影响STAT6从而抑制黏蛋白MUC5AC的表达,抑制支气管哮喘气道黏液高分泌,表明Brg1具有促进哮喘气道黏液高分 泌的作用。
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.

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更新日期/Last Update: 1900-01-01