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

作　　者：丁丽丽 刘轩绮 孙晓林 高雅静 武志慧 王永福[1] DING Lili;LIU Xuanqi;SUN Xiaolin;GAO Yajing;WU Zhihui;WANG Yongfu(Department of Rheumatic Immunology,the First Affiliated Hospital of Baotou Medical College,Baotou,Inner Mongolia,014010;Central Laboratory,Key Laboratory of Autoimmunity in the Inner Mongolia Autonomous Region,the First Affiliated Hospital of Baotou Medical College,Baotou,Inner Mongolia,014010)

机构地区：[1]包头医学院第一附属医院风湿免疫科,内蒙古包头014010 [2]包头医学院第一附属医院中心实验室/内蒙古自治区自体免疫学重点实验室,内蒙古包头014010

出　　处：《实用临床医药杂志》2022年第14期7-13,共7页Journal of Clinical Medicine in Practice

基　　金：国家自然科学基金资助项目(81860294);内蒙古自治区自然科学基金资助项目(2019MS08055)。

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。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-βwere 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-βmay 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.

关 键 词：转化生长因子-Β 系统性硬化症相关间质性肺病 特发性肺纤维化 生物信息学分析 

分 类 号：R563[医药卫生—呼吸系统] R392.1[医药卫生—内科学]