Xia Xinyi, Fan Xinrui, Jiang Shan, Liao Yuhan, Sun Yang
Department of Cardiology, Union Hospital, Huazhong University of Science and Technology and Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Tongji Medical College, Wuhan, China.
Faculty of Psychology, Sleep and NeuroImaging Center, Southwest University, Chongqing, China.
PLoS One. 2024 Dec 23;19(12):e0311661. doi: 10.1371/journal.pone.0311661. eCollection 2024.
Although the link between ischemia-reperfusion injury (IRI) and T cell-mediated rejection (TCMR) in kidney transplantation (KT) is well known, the mechanism remains unclear. We investigated essential genes and biological processes involved in interactions between IRI and TCMR.
Renal IRI and TCMR datasets were obtained from the Gene Expression Omnibus database. IRI and TCMR co-expression networks were built using weighted gene co-expression network analysis, and essential modules were identified to acquire shared genes and conduct functional enrichment analysis. Shared genes were used for TCMR consensus clustering, differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was conducted. Three machine learning algorithms screened for hub genes, which underwent miRNA prediction and transcription factor analysis. Hub gene expression was verified, and survival analysis was performed using Kaplan-Meier curves.
IRI and TCMR shared 84 genes. Functional enrichment analysis revealed that inflammation played a significant role. Based on shared genes, TCMR was divided into two clusters. GSEA revealed that graft rejection-related pathways varied between the two clusters. TCMR hub genes, guanylate-binding protein 1 (GBP1) and CD69, showed increased expression. Decreased survival rates were found in patients who had undergone KT and had high GBP1 and CD69 levels.
The study demonstrates that renal IRI has a potential role in renal TCMR and the pathogenic pathways are potentially inflammation-related.
尽管肾移植（KT）中缺血再灌注损伤（IRI）与T细胞介导的排斥反应（TCMR）之间的联系已为人熟知，但其机制仍不清楚。我们研究了IRI与TCMR相互作用中涉及的关键基因和生物学过程。
从基因表达综合数据库中获取肾脏IRI和TCMR数据集。使用加权基因共表达网络分析构建IRI和TCMR共表达网络，识别关键模块以获取共享基因并进行功能富集分析。共享基因用于TCMR共识聚类，鉴定差异表达基因（DEG），并进行基因集富集分析（GSEA）。三种机器学习算法筛选出枢纽基因，对其进行miRNA预测和转录因子分析。验证枢纽基因表达，并使用Kaplan-Meier曲线进行生存分析。
IRI和TCMR共享84个基因。功能富集分析表明炎症起重要作用。基于共享基因，TCMR分为两个簇。GSEA显示两个簇之间与移植物排斥相关的途径有所不同。TCMR枢纽基因鸟苷酸结合蛋白1（GBP1）和CD69表达增加。接受KT且GBP1和CD69水平高的患者生存率降低。
该研究表明肾脏IRI在肾脏TCMR中具有潜在作用，且致病途径可能与炎症相关。
