解放军医学杂志2025，Vol.50Issue(12)：1567-1576,10.DOI:10.11855/j.issn.0577-7402.1921.2025.0918
小鼠肾缺血再灌注损伤与自噬相关的差异表达基因分析及其靶基因网络构建
Analysis of autophagy-related differentially expressed genes in murine renal ischemia-reperfusion injury and network construction of target genes
摘要
Abstract
Objective To screen autophagy-related hub genes in renal ischemia-reperfusion injury(RIRI)and analyze their biological functions to investigate the pathogenesis of RIRI.Methods Twelve ICR mice were randomly assigned to control group and RIRI group(n=6 per group).Renal tissues from both groups were subjected to transcriptome sequencing.After quality control filtering,differentially expressed genes(DEGs)between the two groups were identified.The intersection of these DEGs with autophagy-related genes(ATGs)yielded autophagy-related DEGs(ATG-DEGs).Hub genes were selected as the top-ranked ATG-DEGs using four algorithms in Cytohubba.Gene set enrichment analysis(GSEA)was performed for the hub genes.Two murine RIRI-related gene expression datasets were downloaded from the Gene Expression Omnibus(GEO)database for single-cell RNA-seq analysis to identify key genes at the single-cell level,followed by immune infiltration analysis.Finally,the expression levels of hub genes in mice were detected using quantitative real-time polymerase chain reaction(qRT-PCR).Results A total of 672 DEGs were identified between the two groups.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses suggested that these DEGs might be associated with autophagy.Six hub genes were identified:phagocytic glycoprotein-1(Cd44),integrin subunit alpha M(Itgam),integrin subunit alpha X(Itgax),kinase insert domain receptor(Kdr),secreted phosphoprotein 1(SPP1),and glyceraldehyde-3-phosphate dehydrogenase(GAPDH).These genes were involved in signaling pathways related to oxidative stress,inflammatory response,apoptosis,and immune response.Based on the murine RIRI-related data downloaded from the GEO database,single-cell transcriptome analysis revealed that two hub genes(Cd44 and Itgam)were highly expressed in neutrophils,macrophages,and fibroblasts in RIRI group compared with control group(P<0.05).Cd44+neutrophils and Itgam+macrophages exhibited more active cell communication.Immune infiltration results showed the correlations of Cd44 and Itgam with neutrophils and macrophages were higher in RIRI group than those in control group.qRT-PCR results confirmed that the expression levels of Cd44 and Itgam were significantly higher in RIRI group than those in control group(P<0.05).Conclusion Cd44 and Itgam are autophagy-related hub genes in murine RIRI and may serve as novel biomarkers for the prevention and treatment of RIRI.关键词
肾缺血再灌注损伤/生物信息学/枢纽基因/吞噬细胞糖蛋白-1/整联蛋白αMKey words
renal ischemia-reperfusion injury/bioinformatics analysis/hub genes/phagocytic glycoprotein-1/integrin subunit alpha M分类
医药卫生引用本文复制引用
Xie Long-Yu,Zhong Yi,Liu Lei,Min Jie-Yu,An Li..小鼠肾缺血再灌注损伤与自噬相关的差异表达基因分析及其靶基因网络构建[J].解放军医学杂志,2025,50(12):1567-1576,10.基金项目
This work was supported by the Project for the Growth of Young Scientific and Technological Talents in Regular Higher Education Institutions of Guizhou Province(QJHKYZ2022234),and the Key Laboratory Fund of Guizhou Medical University(2024fy003) 贵州省普通高等学校青年科技人才成长项目(黔教合KY字[2022]234号) （QJHKYZ2022234）
贵州医科大学校级重点实验室基金([2024]fy003) （[2024]fy003）
