特发性肺纤维化和炎症性肠病共同核心基因特征及其生物学机制的鉴定  

Identification of the Shared Hub Gene Signatures and Biological Mechanism in Idiopathic Pulmonary Fibrosis and Inflammatory Bowel Disease

作　　者：娄娇娇 王浩冉 黄凤祥[1] 王焕勤[1] 康燕[1] 王起龙 马开 乔瑞萍 苗丽君[1] LOU Jiaojiao;WANG Haoran;HUANG Fengxiang;WANG Huanqin;KANG Yan;WANG Qilong;MA Kai;QIAO Ruiping;MIAO Lijun(Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院呼吸与危重症医学科,河南郑州450052

出　　处：《河南医学研究》2024年第5期772-779,共8页Henan Medical Research

摘　　要：目的基于生物信息学研究介导特发性肺纤维化(IPF)和炎症性肠病(IBD)共存的潜在关键分子和通路。方法通过美国国家生物技术信息中心(NCBI)基因表达综合数据库(GEO)下载IPF(GSE110147)和IBD(GSE752141)数据集。使用R的“limma”包分析差异表达基因(DEGs)。对DEGs进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。利用STRING数据库和Cytoscape软件进行蛋白质-蛋白质相互作用(PPI)网络构建、模块构建和核心基因鉴定。在IPF的GSE53845和IBD的GSE59071数据中对核心基因进行验证。基于NetworkAnalyst Web平台,构建转录因子(TFs)-核心基因与TFs-微小核糖核酸(miRNAs)的相互作用网络。结果筛选出67个上调基因和23个下调基因进行后续分析。利用CytoHubba和MCODE插件鉴定出6个重要的枢纽基因,包括SPP1、COL1A1、POSTN、MMP7、COL3A1和COL6A3。在TFs基因相互作用网络中,SPP1与其他TFs的相互作用率最高。HINFP、POU2F2、YY1、FOXL1和FOXC1协同参与SPP1的调控。另一方面,在TFs-miRNAs共调控网络中的miRNAs,hsa-miR-301b、hsa-miR301a、hsa-miR-29c、hsa-miR-29b和hsa-miR-29a在3个地方表现出最高的程度,并且都靶向COL6A3。结论这项生物信息学研究揭示了IPF和IBD的共同发病机制,表明IPF和IBD是相似的,这可以为进一步的研究提供新的思路。Objective To explore the potential hub molecules and pathways mediating the co-occurrence of idiopathic pulmonary fibrosis(IPF)and inflammatory bowel disease(IBD)based on bioinformatics.Methods Datasets of IPF(GSE110147)and IBD(GSE752141)were downloaded from the National Center for Biotechnology Information(NCBI)gene expression omnibus(GEO).The“limma”packages of R was used to analyze differentially expressed genes(DEGs).The biological functions of the DEGs underwent gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Then,STRING database and Cytoscape software were used for protein-protein interaction(PPI)network,module construction and hub gene identification.Hub gene validation was performed in GSE53845 for IPF and GSE59071 for IBD.Based on the NetworkAnalyst Web platform,an interaction network for TFs-hub genes and TFs-microRNAs(miRNAs)was constructed.Results A total of 67 up-regulated genes DEGs and 23 down-regulated genes DEGs were screened out for follow-up analyses.Six important hub genes,including SPP1,COL1A1,POSTN,MMP7,COL3A1,COL6A3 were identified using CytoHubba and MCODE plugin.In the TFs-gene interaction network,SPP1 had the highest interaction rate with other TFs genes.Among the regulatory factors with the highest degree of TFs-genes interaction network,HINFP,POU2F2,YY1,FOXL1 and FOXC1 coordinately take part in the regulation of SPP1.On the other hand,among the miRNAs in the TFs-MiRNAs co-regulatory network,hsa-miR-301b,hsa-miR-301a,hsa-miR-29c,hsa-miR-29b and hsa-miR-29a showed the highest degree at three places,and all of them targeted COL6A3.Conclusion This bioinformatics study reveals the common pathogenesis of IPF and IBD,suggesting that IPF and IBD are similar,which can provide new ideas for further research.

关 键 词：特发性肺纤维化 炎症性肠病 核心基因 转录因子 微小核糖核酸 

分 类 号：R563[医药卫生—呼吸系统]