Department of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Hereditas. 2022 Jun 4;159(1):24. doi: 10.1186/s41065-022-00236-x.
Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods.
We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks.
A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine.
Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.
缺血/再灌注损伤-急性肾损伤（IRI-AKI）的机制尚未完全阐明。我们通过生物信息学方法对 IRI-AKI 进行综合分析。
我们从基因表达综合数据库（GEO）中筛选了 IRI-AKI 早期阶段的基因表达谱。基于基因本体（GO）、京都基因与基因组百科全书（KEGG）数据库和基因集富集分析（GSEA）进行差异表达基因（DEGs）鉴定和富集途径分析。进行免疫细胞浸润分析以揭示微环境细胞类型的变化。我们构建了蛋白质-蛋白质相互作用（PPI）网络，并使用 Cytoscape 插件寻找枢纽基因和模块。我们进行了稳健秩聚合（RRA）以结合 DEGs，并分析了 miRNA/转录因子（TF）和药物-基因相互作用网络的靶基因。
在 GSE87024 和 GSE34351 中分别鉴定出 239 个和 384 个 DEGs，有 73 个共同 DEGs。富集分析显示，显著途径涉及丝裂原活化蛋白激酶（MAPK）信号、白细胞介素-17 和肿瘤坏死因子（TNF）信号通路等。RRA 分析共检测到 27 个共同 DEGs。免疫细胞浸润分析显示，在 IRI-AKI 中浆细胞减少，T 细胞增加。我们确定 JUN、ATF3、FOS、EGR1、HMOX1、DDIT3、JUNB、NFKBIZ、PPP1R15A、CXCL1、ATF4 和 HSPA1B 为枢纽基因。靶基因与 23 个 miRNA 和 116 种药物或分子化合物相互作用，如姜黄素、星孢菌素和去铁胺。
我们的研究首次采用 RRA 分析，结合不同数据集的 DEGs，聚焦于早期 IRI-AKI。我们确定了参与 IRI-AKI 的重要生物标志物和关键途径，并首次构建了免疫图谱，通过药物-基因网络检测到 IRI-AKI 的潜在治疗靶点。
