系统性硬化症相关间质性肺病、特发性肺纤维化与转化生长因子-β诱导的肺纤维化模型重叠基因的相关性分析

Analysis in relationships of overlapping genes in systemic sclerosis-associated interstitial lung disease, idiopathic pulmonary fibrosis and pulmonary fibrosis model induced by transforming growth factor-β

  • 摘要:
    目的 利用生物信息学技术分析系统性硬化症相关间质性肺病(SSc-ILD)、特发性肺纤维化(IPF)与转化生长因子-β(TGF-β)诱导的肺纤维化模型重叠基因的相关性。
    方法 通过Gene Expression Omnibus(GEO)数据库获取SSc-ILD、IPF与TGF-β诱导的肺纤维化模型相关基因芯片数据GSE76808、GSE135099。采用R软件对数据进行分析,按照adj.P<0.05和|logFC|>1进行筛选,将筛选得到的基因进行基因交互分析;利用R软件对重叠基因进行基因本体(GO)功能注释、京都基因与基因组百科全书(KEGG)通路富集及可视化;基于String数据库对重叠基因进行蛋白质互作(PPI)分析;应用在线分析工具TISIDB获得hub基因并分析其功能。
    结果 与健康对照组(NC组)相比,SSc-ILD、IPF、TGF-β诱导的肺纤维化模型中存在差异性表达的基因。在SSc-ILD、IPF、TGF-β诱导的肺纤维化模型均下调的34个重叠基因中存在PPI并获得hub基因ELAVL1。GO富集分析结果表明,ELAVL1基因不仅参与RNA剪接、加工、翻译等多种转录后修饰过程,还在腺苷酸活化蛋白激酶(AMPK)信号通路中存在富集。
    结论 在SSc-ILD和IPF两种疾病中,AMPK信号可能存在异常,导致TGF-β产生增多,而TGF-β可能通过调控ELAVL1蛋白(HuR)由胞核向胞浆转位,进而参与肺纤维化的调节,但具体机制仍有待进一步验证。

     

    Abstract:
    Objective To analyze the relationships of overlapping genes in systemic sclerosis-associated interstitial lung disease (SSc-ILD), idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis model induced by transforming growth factor-β (TGF-β) by using bioinformatics technology.
    Methods Relevant gene chip data GSE76808 and GSE135099 of SSc-ILD, IPF and pulmonary fibrosis model induced by TGF-β were obtained from Gene Expression Omnibus (GEO) database. R software was used to analyze the data, and according to the screening conditions of adj. P<0.05 and |logFC|>1, the screened genes were analyzed by gene interaction; Gene Ontology (GO) function annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and visualization for overlapping genes were performed by using R software; protein-protein interaction (PPI) analysis of overlapping genes was performed based on string database; the hub gene was obtained by analysis tool TISIDB and its function was analyzed.
    Results Compared with the normal control group (NC group), there were differentially expressed genes in SSc-ILD, IPF and pulmonary fibrosis model induced by TGF-β. There was PPI existed in 34 overlapping genes down-regulated by SSc-ILD, IPF and pulmonary fibrosis model induced by TGF-β, and hub gene ELAVL1 was obtained. GO enrichment analysis results showed that ELAVL1 gene was not only involved in many post-transcriptional modification processes such as RNA splicing, processing and translation, but also enriched in adenylate activated protein kinase (AMPK) signal pathway.
    Conclusion In SSc-ILD and IPF, the AMPK signal may be abnormal, resulting in increasing of TGF-β, and TGF-β may be involved in the regulation of pulmonary fibrosis by regulating the translocation of ELAVL1 protein (HuR) from nucleus to cytoplasm, but the specific mechanism still needs to be further verified.

     

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