线粒体相关基因在特发性肺纤维化中的分析  

Analysis of mitochondrial related genes in idiopathic pulmonary fibrosis

作　　者：吴沛玲 娄月妍[1] 张洪艳 陈东方 刘雪青 赵丽芳 薛姗 蒋捍东[1] Wu Peiling;Lou Yueyan;Zhang Hongyan;Chen Dongfang;Xue Shan;Zhao Lifang;Liu Xueqing;Jiang Handong(Department of Respiratory and Critical Care Medicine,Renji Hospital of Shanghai Jiao Tong University School of Medicine,Shanghai 200120,China)

机构地区：[1]上海交通大学医学院附属仁济医院呼吸与危重症医学科,上海200120

出　　处：《中华肺部疾病杂志（电子版）》2024年第2期178-184,共7页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金项目资助(82173828)。

摘　　要：目的通过生物信息学方法和肺纤维化(idiopathic pulmonary fibrosis,IPF)小鼠模型分析与特发性肺纤维化发生发展相关的线粒体相关基因。方法从基因表达综合数据库(gene expression omnibu,GEO)中获得IPF样本和正常样本间的差异表达基因;通过MitoCarta3.0数据库和所得差异基因进行匹配,以获取线粒体相关差异基因(mitochondrial-related differential expressed genes,MiRDEGs),并对其进行基因本体论(GeneOntology,GO)分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)功能富集分析;构建MiRDEGs的PPI网络,并使用Cytohubba获得核心MiRDEGs;建立肺纤维化小鼠模型验证鉴定出的核心MiRDEGs。结果最终得到26个上调的MiRDEGs和24个下调的MiRDEGs,主要涉及到有氧呼吸,线粒体结构和物质代谢。其中10个MiRDEGs被cytohubba鉴定为核心MiRDEGs。结果表明,在小鼠肺纤维化模型中,FASN,PDK4,ACSL1的表达低于对照组,而ALDH18A1,MTHFD2,ALDH1L2,PC的表达则高于对照组。结论IPF中的线粒体相关基因及其对免疫浸润的影响与IPF的发病相关并可能为潜在的治疗靶点。Objective Mitochondria-related genes associated with the development of idiopathic pulmonary fibrosis were analyzed by bioinformatics methods and the pulmonary fibrosis mouse model.Methods Datasets were acquired from the GEO database.Analysis of differential expressed genes(DEGs)was conducted for each dataset using the GEO2R online tool.Mitochondrial-related differential expressed genes(MiRDEGs)were identified by intersecting MitoCarta3.0 database genes with DEGs.Subsequently,functional enrichment analyses and a Protein-Protein Interaction(PPI)network construction were conducted for MiRDEGs,with hub MiRDEGs identified using CytoHubba.Mouse model of bleomycin-induced pulmonary fibrosis were used to validate hub MiRDEGs.Results Our study identified 26 upregulated and 24 downregulated MiRDEGs linked to mitochondrial function,structure and metabolism pathways.Cytohubba identified 10 hub MiRDEGs.Immune infiltration analysis indicated abundant M 2 macrophage,M 1 macrophage,and M 0 macrophage infiltration in IPF samples.Notably,among the hub MiRDEGs,ACSL1 exhibited the most pronounced negative correlation with M 2 macrophage infiltration,while PC showed the strongest positive correlation.Animal experiments demonstrated that lower expression of FASN,PDK4,and ACSL1,and higher expression of ALDH18A1,MTHFD2,ALDH1L2,and PC in the pulmonary fibrosis mouse model compared to the control group.Conclusion By comprehensively exploring the genes related to mitochondria and emphasizing their impact on immune infiltration in IPF,this investigation provides insights into the molecular mechanisms underlying IPF and potential therapeutic target.

关 键 词：特发性肺纤维化 线粒体 免疫 生物信息学 

分 类 号：R563[医药卫生—呼吸系统]