Wang Shili, Pan Xingyu, Peng Jinpu, Wu Moudong, Zhan Xiong, Wang Wei, Zhu Guohua, An Nini, Pei Jun
Department of Pediatric Urology, Guizhou Branch of Shanghai Children's Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, China.
Department of Pediatric surgrey, Guizhou Provincial People's Hospital, Guiyang, China.
Ren Fail. 2025 Dec;47(1):2532856. doi: 10.1080/0886022X.2025.2532856. Epub 2025 Jul 27.
The study aims to investigate the role and significance of macrophage-related genes in peripheral blood during acute renal transplant rejection.
Based on the dataset GSE15296, differential genes (DEGs) were intersected with macrophage-associated genes (MAGs), which defined as macrophage-associated genes (DEMAGs). Subsequently, GO and KEGG enrichment analyses were performed on DEMAGs. The PPI protein interaction network and machine learning were applied to identify Hub genes, which were also validated by GSE46474, an external validation set. We constructed a rat model of acute rejection of kidney transplantation and sequenced the transcriptome of the serum, and using the sequencing results, we analyzed the expression levels of the Hub gene. Then, a correlation analysis was carried out based on the Hub genes and different immune cell infiltration levels. Finally, GRNdb, miRDB, and GeneCards databases were applied to study the transcription factors, miRNAs, and regulatory drugs of Hub genes, respectively.
The results of the Cibersort analysis revealed that M2-type macrophages were expressed higher in the Normal group. In addition, the results of the correlation analysis suggested that the expressions of Hub genes were negatively correlated with M1-type macrophages and positively correlated with M2-type macrophages.
A diagnostic model of the macrophage-associated acute renal transplant rejection in peripheral blood was constructed based on CCR2 and TLR3, which can accurately diagnose the biological alterations of acute kidney transplant rejection. Meanwhile, these two Hub genes may become potential therapeutic targets in acute rejection of kidney transplantation.
本研究旨在探讨巨噬细胞相关基因在急性肾移植排斥反应外周血中的作用及意义。
基于数据集GSE15296，将差异基因（DEGs）与巨噬细胞相关基因（MAGs）进行交集分析，定义为巨噬细胞相关差异基因（DEMAGs）。随后，对DEMAGs进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。应用蛋白质-蛋白质相互作用（PPI）网络和机器学习来识别枢纽基因，并通过外部验证集GSE46474进行验证。我们构建了大鼠肾移植急性排斥反应模型并对血清转录组进行测序，利用测序结果分析枢纽基因的表达水平。然后，基于枢纽基因和不同免疫细胞浸润水平进行相关性分析。最后，分别应用基因调控网络数据库（GRNdb）、微小RNA数据库（miRDB）和基因卡片数据库（GeneCards）研究枢纽基因的转录因子、微小RNA和调控药物。
Cibersort分析结果显示，M2型巨噬细胞在正常组中表达较高。此外，相关性分析结果表明，枢纽基因的表达与M1型巨噬细胞呈负相关，与M2型巨噬细胞呈正相关。
基于CCR2和TLR3构建了外周血巨噬细胞相关急性肾移植排斥反应的诊断模型，该模型可准确诊断急性肾移植排斥反应的生物学改变。同时，这两个枢纽基因可能成为肾移植急性排斥反应的潜在治疗靶点。
