Identification of core targets and construction of diagnostic models for ischemia-reperfusion injury in donor kidneys from different sources
10.12464/j.issn.1674-7445.2026104
- VernacularTitle:不同来源供肾缺血-再灌注损伤核心靶点的鉴定和诊断模型的构建
- Author:
Jun PEI
1
;
Jinpu PENG
1
;
Moudong WU
1
;
Hongyu TANG
1
;
Nini AN
1
;
Xingyu PAN
2
Author Information
1. Department of Pediatric Surgery, Guizhou Provincial People's Hospital, Guiyang 550002, China.
2. null.
- Publication Type:OriginalArticle
- Keywords:
Kidney transplantation;
Ischemia-reperfusion injury;
Living donor;
Donor after brain death;
Donation after circulatory death;
Neutrophil extracellular trap;
Glutathione;
Immune cell infiltration
- From:
Organ Transplantation
2026;17(5):807-816
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the potential functional targets of ischemia-reperfusion injury (IRI) in renal allografts derived from different donor sources. Methods Based on the transcriptome sequencing dataset GSE43974 of kidney transplantation IRI from different donor sources, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed to screen Hub genes and characterize their expression profiles. A nomogram model was established to evaluate the diagnostic efficacy of these Hub genes, which was further validated using the dataset GSE30718. Immune infiltration analysis was conducted to clarify the correlations between Hub genes and immune cell infiltration. A mouse kidney transplantation IRI model was adopted to verify the expression levels of Hub genes in vivo. Results A total of five Hub genes were finally identified, namely PPP1CC, GART, BIRC6, PMSD11 and TMEM192. Nomogram analysis confirmed that these Hub genes possessed favorable diagnostic performance for kidney transplantation IRI in kidneys from different donors. Immune infiltration analysis revealed distinct infiltration patterns of various immune cells in IRI kidneys from different donors, and Hub genes were closely correlated with the regulation of multiple immune cell infiltration. A total of 390 differentially expressed genes were screened between renal tissues of mice in the kidney transplantation group and sham operation group. Gene Ontology (GO) enrichment analysis indicated that these differentially expressed genes were mainly enriched in biological processes including oxidative stress, inflammation and pyroptosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed significant enrichment in glutathione metabolism, neutrophil extracellular trap formation and other signaling pathways. Transcriptome sequencing verified that the expression levels of the five Hub genes were significantly different between the two groups (all P < 0.05). Conclusions Five Hub genes are identified in kidney transplantation IRI using donor kidneys from different sources. Glutathione metabolism and neutrophil extracellular trap formation may participate in the pathogenesis of kidney transplantation IRI.
