PDE4D在哮喘患儿和哮喘模型的表达差异
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江苏省青年医学人才项目(QNRC2016087);南京市科委(社发)(201723003);南京市卫计委重点项目(ZKX18041)


Expression differences of PDE4D in asthmatic children and asthmatic models
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    摘要:

    目的:筛选哮喘相关候选基因,并在人群和动物水平验证。方法:从高通量基因表达数据库(gene expression omnibus,GEO)搜索哮喘痰相关基因芯片数据,利用GEO 2R筛选表达差异基因,并参考全基因关联分析(genome-wide association study,GWAS)筛选哮喘相关基因,收集哮喘患儿及同期健康儿童痰标本,构建小鼠哮喘模型、大鼠肥大细胞株(RBL-2H3)哮喘模型,应用RT-PCR进行验证。结果:共纳入2套哮喘痰基因芯片数据,选出有交集的差异表达基因190个,结合GWAS最终筛选出哮喘相关基因磷酸二酯酶4D(PDE4D)。进一步验证PDE4D在哮喘患儿痰样本中表达上调(P < 0.05),但在哮喘小鼠模型整个肺组织中表达下调(P < 0.05),而在致敏的RBL-2H3细胞中表达上调(P < 0.05)。结论:PDE4D在人群、哮喘小鼠及肥大细胞中存在差异表达,可能作为肥大细胞参与哮喘发展的研究靶点。

    Abstract:

    Objective:This study aims to screen for asthma-related candidate genes and validate at the population and animal levels to explore the pathogenesis of asthma. Methods:The asthma-related sputum chip was searched from Gene Expression Omnibus(GEO),the differentially expressed genes were screened by GEO 2R,and the asthma-related genes were screened by reference to the whole gene association analysis(GWAS). Asthmatic children and healthy children’s sputum specimens werecolle cted. Mouse asthma model construct and rat mast cell strain(RBL-2H3)asthma model were constructed,and real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used for differential expression verification. Results:Two sets of asthmatic gene chip data were included,and 190 differentially expressed genes with crossovers were selected. GWAS was used to finally screen out the asthma-related gene PDE4D. It was further verified that the expression of PDE4D was increased in the sputum samples of asthmatic children(P < 0.05),and decreased in the whole lung tissue of the asthma mouse model(P < 0.05),but up-regulated in the sensitized RBL-2H3 cells(P < 0.05). Conclusion:PDE4D is differentially expressed in human,asthmatic mice and mast cells,which may serve as a research target for mast cells to participate in the development of asthma.

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张秀青,于春琳,刘 峰,赵德育. PDE4D在哮喘患儿和哮喘模型的表达差异[J].南京医科大学学报(自然科学版),2019,(11):1561-1566

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  • 收稿日期:2019-02-17
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  • 在线发布日期: 2019-12-02
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