Comprehensive analysis of necroptosis-related genes in renal ischemia-reperfusion injury

Abstract

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.

ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms

“…Kidney IR injury is common in renal surgery and results in acute kidney injury, chronic kidney disease, and kidney fibrosis, eventually inducing kidney dysfunction. Recent studies have revealed that the renal IR injury was mediated by activated inflammation, apoptosis, and ferroptosis . MSC therapy is widely studied due to its ability to reduce inflammation in IR areas.…”

“…Recent studies have revealed that the renal IR injury was mediated by activated inflammation, apoptosis, and ferroptosis. 44 MSC therapy is widely studied due to its ability to reduce inflammation in IR areas. However, the efficacy of MSC therapy on IR-related diseases in clinical research is unsatisfactory, partially because it cannot effectively inhibit cell death such as ferroptosis and apoptosis.…”