[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

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    • Source:
      Publisher: Zhonghua yi xue hui Country of Publication: China NLM ID: 7511141 Publication Model: Print Cited Medium: Print ISSN: 0376-2491 (Print) Linking ISSN: 03762491 NLM ISO Abbreviation: Zhonghua Yi Xue Za Zhi Subsets: MEDLINE
    • Publication Information:
      Publication: Beijing : Zhonghua yi xue hui
      Original Publication: Beijing : Zhonghua yi xue hui.
    • Subject Terms:
    • Abstract:
      Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.
    • Contributed Indexing:
      Local Abstract: [Publisher, Chinese] 目的: 筛选支气管哮喘核心差异表达基因并对其进行生物信息学分析。 方法: 从基因表达数据库(GEO)下载哮喘患者巨噬细胞基因芯片数据GSE22528,该数据集包括了10份人肺泡灌洗液的转录组信息,其中哮喘患者和对照个体各5份。采用R 4.0.4软件筛选差异表达基因(DEGs)。利用DAVID 6.8数据库对筛选出的DEGs进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。利用STRING在线数据库对DEGs编码蛋白构建蛋白互作网络(PPI),采用Cytoscape软件构建核心模块并确定核心DEGs。 结果: 肺泡灌洗液标本均来自加拿大白种人,哮喘患者和对照个体年龄范围分别为20~37和18~36岁,各组男性均为3例。哮喘患者上调基因449个,下调基因47个。GO分析显示:哮喘患者上调基因主要涉及对未折叠蛋白的反应等生物过程,分子功能集中于未折叠蛋白和生长因子的绑定;下调基因主要涉及组蛋白脱乙酰作用和泛素介导的蛋白质降解等生物过程,分子功能集中于组蛋白脱乙酰酶活性。KEGG通路富集分析显示:通路主要由上调基因富集,涉及Hippo信号通路、肥厚型心肌病、雌激素信号通路、致心律失常性右心室心肌病、基底细胞癌、神经活化的受体配体相互作用、扩张型心肌病和黏附连接等信号通路。PPI分析共得到两个核心模块,筛选出14个核心DEGs,分别为促黑色素聚集激素(PMCH)、孤啡肽前体(PNOC)、鞘氨醇-1-磷酸受体2(S1PR2)、鞘氨醇-1-磷酸受体5(S1PR5)、CC型趋化因子配体21(CCL21)、Kelch样蛋白25(KLHL25)、泛素结合酶E2V2(UBE2V2)、F-box蛋白17(FBXO17)、味觉受体2型成员3(TAS2R3)、生长抑素受体2(SSTR2)、代谢型谷氨酸受体2(GRM2)、李斯特E3泛素蛋白连接酶1(LTN1)、LIM域特有蛋白7(LMO7)和环指蛋白19A基因(RNF19A),其中LTN1和UBE2V2下调,其余均上调。 结论: 哮喘患者与对照个体存在DEGs、PMCH、PNOC、S1PR2、S1PR5和CCL21基因等可能为哮喘发病机制中的核心基因。.
    • Accession Number:
      EC 2.3.2.27 (RNF19A protein, human)
      EC 2.3.2.27 (Ubiquitin-Protein Ligases)
    • Publication Date:
      Date Created: 20211213 Date Completed: 20211214 Latest Revision: 20211214
    • Publication Date:
      20240829
    • Accession Number:
      10.3760/cma.j.cn112137-20210607-01293
    • Accession Number:
      34895422