基于生物信息学分析小鼠急性肾损伤和急性肺损伤的枢纽基因  

Bioinformatics analysis of hub genes of acute kidney injury and acute lung injury in mice

作　　者：林玲 李京儒 沈瑞华 林惠 乔晞[1,2,3,4] Lin Ling;Li Jingru;Shen Ruihua;Lin Hui;Qiao Xi(Department of Nephrology,Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Shanxi Kidney Disease Institute,Taiyuan 030001,Shanxi Province,China;Kidney Research Center of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学第二医院肾内科,太原030001 [2]山西医科大学,太原030001 [3]山西省肾脏病研究所,太原030001 [4]山西医科大学肾脏疾病研究中心,太原030001

出　　处：《中华肾病研究电子杂志》2024年第3期134-144,共11页Chinese Journal of Kidney Disease Investigation（Electronic Edition）

基　　金：国家自然科学基金资助项目(81970643);山西省海外归国人员科学活动基金项目(2017-29);中国山西省留学基金委资助课题(2020-186)。

摘　　要：目的基于生物信息学方法对小鼠急性肾损伤(AKI)和急性肺损伤(ALI)进行基因表达谱数据挖掘,旨在探讨AKI和ALI之间关系。方法从基因表达综合数据库(GEO)中分别下载AKI和ALI基因表达谱,去除批次效应后进行差异分析。利用基因本体(GO)和京都基因和基因组百科全书(KEGG)数据库对AKI和ALI的差异表达基因(DEGs)进行富集分析。使用STRING数据库构建蛋白-蛋白相互作用(PPI)网络后,检测网络的核心模块和枢纽基因。通过使用Cytoscape插件的算法获得最佳枢纽基因后,进行免疫细胞浸润分析。结果AKI和ALI建模后4~6 h、24 h分别筛选出交集DEGs为114个、62个,GO和KEGG通路富集分析提示其与免疫应答和炎症信号通路有关。进一步分析,在AKI和ALI建模后4~6 h筛选出5个最佳枢纽基因,包括IL-6、IL-1β、CCL2、TLR2和CXCL10;AKI和ALI建模后24 h筛选出5个最佳枢纽基因,包括IL-6、IL-1β、TNF、TLR2和CXCL10。在AKI建模后4~6 h,枢纽基因表达与中性粒细胞和M1巨噬细胞呈正相关,而与记忆CD4+T细胞、记忆CD8^(+)T细胞呈负相关。在ALI建模后4~6 h,枢纽基因表达与树突状细胞和单核细胞呈正相关,而与未成熟树突状细胞和嗜酸性粒细胞呈负相关。在AKI建模后24 h,枢纽基因表达与中性粒细胞呈正相关,而与初始B细胞和调节性T细胞呈负相关。在ALI建模后24 h,枢纽基因表达与M1、M2巨噬细胞和中性粒细胞等呈正相关,而与初始CD8^(+)T细胞和嗜酸性粒细胞呈负相关。结论小鼠AKI和ALI建模后4~6 h和24 h具有相似的枢纽基因和信号通路,两种疾病分子机制密切相关,尚需深入研究以探讨潜在的治疗靶点。Objective Data mining of gene expression profiles of acute kidney injury(AKI)and acute lung injury(ALI)in mice was conducted based on bioinformatics analysis in order to study the relationship between AKI and ALI.Methods AKI and ALI gene expression profiles were downloaded from the Gene Expression Omnibus(GEO)database.After the batch effect was removed,difference analysis was performed.Enrichment analysis of differentially expressed genes(DEGs)in AKI and ALI with the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The STRING database was used to build a protein-protein interaction(PPI)network in which the core modules and hub genes were detected.The best hub genes were obtained by using six algorithms from Cytoscape′s plugin cytoHubba.Finally,Immune cell infiltration analysis was conducted to analyze the relationship between optimal hub genes and immune cells.Results A total of 114 overlapping DEGs were screened out at 4-6 h after establishment of AKI and ALI.A total of 62 overlapping DEGs were screened out at 24 h after establishment of AKI and ALI.The GO and KEGG enrichment analysis suggested that the overlapping DEGs were mainly related to immune and inflammatory signaling pathways.Finally,five optimal hub genes including IL-6,IL-1β,CCL2,TLR2,and CXCL10 were screened out at 4-6 h after establishment of AKI and ALI.Besides,five optimal hub genes including IL-6,IL-1β,TNF,TLR2,and CXCL10 were also screened out at 24 h after establishment of AKI and ALI.At 4-6 h after establishment of AKI,the hub genes expression were positively correlated with neutrophils and M1 macrophages,but negatively correlated with memory CD4^(+)T cells and memory CD8^(+)T cells.At 4-6 h after establishment of ALI,expression of the hub genes were positively correlated with dendritic cells and monocytes,but negatively correlated with immature dendritic cells and eosinophils.At 24 h after establishment of AKI,expression of the hub genes were positively correlated with neutrophils,and negatively correlated with

关 键 词：急性肾损伤 急性肺损伤 富集分析 蛋白-蛋白相互作用网络 免疫细胞浸润 

分 类 号：R692[医药卫生—泌尿科学]