OBJECTIVE:This experiment was designed to investigate the effect and mechanism of Brg1(Brahma-related gene 1)on mucus hypersecretion in the airways of asthmatic mice.METHODS:Female C57bl/6 mice aged 68 weeks were randomly divided into four groups:Control group、Asthma group、Brg1-/-group and Brg1-/-+Asthma group(10 in each group).Brg1-/-mouse was knocked down of Brg1 gene in type II alveolar epithelial cells(AEC2s)in C57bl/6mice.Asthma group and Brg1-/-+Asthma group were sensitized with ovalbumin(OVA)to established C57bl/6 mouse asthma model.The number of goblet cells and mucus in airways were stained by PAS staining and real-time PCR was to detect the level of MUC5AC mRNA in lung tissues.MucinMUC5ACandIL-13wasdetectedbyELISAand immunohistochemistry in BALF of lung tissues.The expression of STAT6and p-STAT6 were detected by Western blot analyses.RESULTS:Compared with control group,Asthma group induced airway mucus hypersecretion and the increase of MUC5AC mRNA.The expression of IL-13 and MUC5AC in BALF were significantly higher than those of the controls,as well as the activation of p-STAT6 in lung tissues(P<0.05).However,When the Brg1 gene was knocked down in AEC2s in C57bl/6 mice,the airway mucus and MUC5AC mRNA were reduced.The expression of IL-13 and MUC5AC in BALF,p-STAT6 in lung tissues were also significantly down-regulated(P<0.05).CONCLUSION:The effect of knocking down of Brg1 gene in AEC2s in C57bl/6 mice alleviates bronchial asthma airway mucus hypersecretion and reduces the expression of MUC5AC,which may be explained by inhibiting STAT6 activation.These Suggest Brg1 can promote asthma airway mucus hypersecretion. |