Analysis and Verification of Glycosylation Characteristics of Septic Acute Kidney Injury

作者全名："Chen, Si; Gan, Hua"

作者地址："[Chen, Si; Gan, Hua] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Gan, H (通讯作者)，Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：JOURNAL OF INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001118579700001

JCR分区：Q2

影响因子：4.2

年份：2023

卷号：16

期号：　

开始页：5881

结束页：5897

文献类型：Article

关键词：acute kidney injury; sepsis; glycosylation; hub genes; bioinformatics

摘要："Background: Septic acute kidney injury (S-AKI) results from an imbalance in the regulation of systemic inflammatory responses. Glycosylation plays an important role in inflammatory responses. However, the relationship between S-AKI and glycosylation is unclear.Methods: The datasets of the public platform were analyzed using R language to obtain glycosylation-related differentially expressed genes (GRDEGs) in S-AKI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed for GRDEGs. Hub genes were obtained using three machine learning algorithms and their diagnostic values were evaluated using receiver operating characteristic (ROC) curves. The relationships between the hub genes, immune cells, and signaling pathways were analyzed, and the upstream miRNAs, transcription factors, and compounds of the hub genes were predicted. Mouse models of AKI with sepsis were constructed and the expression of the hub genes was verified. Results: We obtained 45 GRDEGs that were mainly enriched in glycoprotein metabolism and immune inflammatory response, such as ""O-glycan biosynthesis"", ""phagosome"", ""pathogenic Escherichia coli infection"", ""glycosyltransferase activity"", etc. Seven hub genes that have potential diagnostic value were identified and were associated with the regulation of immune cells. Through gene set enrichment analysis (GSEA) of hub genes, it was found that these genes may be involved in metabolism, signaling transduction, and inflammation-related signaling pathways, such as ""metabolism of amino and derivatives"", ""RHO GTPase cycle"", ""transport of small molecules"", ""neutrophil degranulation"", ""immune system"", etc. We then predicted 100 miRNAs, 60 TFs, and 23 compounds of the hub genes using forecasting tools. Finally, animal experiments confirmed the differential expression of ASGR1, UMOD, SPTBN1, and ADAMTS17. Conclusion: This study identified and validated four biomarkers associated with abnormal glycosylation that could be potential targets for AKI in sepsis."

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