期刊论文详细信息
Frontiers in Immunology
Comprehensive analysis of necroptosis-related genes in renal ischemia-reperfusion injury
Immunology
Weixun Zhang1  Shuai Li1  Xiaopeng Hu1 
[1] Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China;Institute of Urology, Capital Medical University, Beijing, China;
关键词: kidney transplantation;    necroptosis;    inflammatory cells;    oxidative stress;    ischemia-reperfusion injury;    delayed graft function;    predictive model;   
DOI  :  10.3389/fimmu.2023.1279603
 received in 2023-08-18, accepted in 2023-10-16,  发布年份 2023
来源: Frontiers
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【 摘 要 】

BackgroundOxidative stress is the primary cause of ischemia-reperfusion injury (IRI) in kidney transplantation, leading to delayed graft function (DGF) and implications on patient health. Necroptosis is believed to play a role in renal IRI. This research presents a comprehensive analysis of necroptosis-related genes and their functional implications in the context of IRI in renal transplantation.MethodsThe necroptosis-related differentially expressed genes (NR-DEGs) were identified using gene expression data from pre- and post-reperfusion renal biopsies, and consensus clustering analysis was performed to distinguish necroptosis-related clusters. A predictive model for DGF was developed based on the NR-DEGs and patients were divided into high- and low-risk groups. We investigated the differences in functional enrichment and immune infiltration between different clusters and risk groups and further validated them in single-cell RNA-sequencing (scRNA-seq) data. Finally, we verified the expression changes of NR-DEGs in an IRI mouse model.ResultsFive NR-DEGs were identified and were involved in various biological processes. The renal samples were further stratified into two necroptosis-related clusters (C1 and C2) showing different occurrences of DGF. The predictive model had a reliable performance in identifying patients at higher risk of DGF with the area under the curve as 0.798. Additionally, immune infiltration analysis indicated more abundant proinflammatory cells in the high-risk group, which was also found in C2 cluster with more DGF patients. Validation of NR-DEG in scRNA-seq data further supported their involvement in immune cells. Lastly, the mouse model validated the up-regulation of NR-DEGs after IR and indicated the correlations with kidney function markers.ConclusionsOur research provides valuable insights into the identification and functional characterization of NR-DEGs in the context of renal transplantation and sheds light on their involvement in immune responses and the progression of IRI and DGF.

【 授权许可】

Unknown   
Copyright © 2023 Li, Zhang and Hu

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