Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China.
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, China.
Biochem Biophys Res Commun. 2024 May 21;709:149790. doi: 10.1016/j.bbrc.2024.149790. Epub 2024 Mar 28.
Macrophages play an important role in the development and progression of acute rejection after kidney transplantation. The study aims to investigate the biological role and significance of macrophage-associated genes (MAG) in acute rejection after kidney transplantation. We utilized transcriptome sequencing results from public databases related to acute rejection of kidney transplantation for comprehensive analysis and validation in animal experiments. We found that a large number of immune-related signaling pathways are activated in acute rejection. PPI protein interaction networks and machine learning were used to establish a Hub gene consisting of TYROBP and TLR8 for the diagnosis of acute rejection. The single-gene GSEA enrichment analysis and immune cell correlation analysis revealed a close correlation between the expression of Hub genes and immune-related biological pathways as well as the expression of multiple immune cells. In addition, the study of TF, miRNAs, and drugs provided a theoretical basis for regulating and treating the Hub genes in acute rejection. Finally, the animal experiments demonstrated once again that acute rejection can aggravate kidney tissue damage, apoptosis level, and increase the release of inflammatory factors. We established and validated a macrophage-associated diagnostic model for acute rejection after kidney transplantation, which can accurately diagnose the biological alterations in acute rejection after kidney transplantation.
巨噬细胞在肾移植后急性排斥反应的发展和进展中起着重要作用。本研究旨在探讨巨噬细胞相关基因（MAG）在肾移植后急性排斥反应中的生物学作用和意义。我们利用公共数据库中与肾移植急性排斥反应相关的转录组测序结果，在动物实验中进行了全面分析和验证。我们发现大量免疫相关信号通路在急性排斥反应中被激活。PPI 蛋白质相互作用网络和机器学习用于建立由 TYROBP 和 TLR8 组成的 Hub 基因，用于急性排斥的诊断。单基因 GSEA 富集分析和免疫细胞相关性分析表明，Hub 基因的表达与免疫相关的生物途径以及多种免疫细胞的表达密切相关。此外，TF、miRNAs 和药物的研究为调节和治疗急性排斥反应中的 Hub 基因提供了理论依据。最后，动物实验再次表明，急性排斥反应会加重肾脏组织损伤、细胞凋亡水平，并增加炎症因子的释放。我们建立并验证了一个用于肾移植后急性排斥反应的巨噬细胞相关诊断模型，该模型可以准确诊断肾移植后急性排斥反应的生物学变化。
