CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection

Background The study aims to investigate the role and significance of macrophage-related genes in peripheral blood during acute renal transplant rejection.Methods Based on the dataset GSE15296, differential genes (DEGs) were intersected with macrophage-associated genes (MAGs), which defined as macro...

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Main Authors: Shili Wang, Xingyu Pan, Jinpu Peng, Moudong Wu, Xiong Zhan, Wei Wang, Guohua Zhu, Nini An, Jun Pei
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2532856
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author Shili Wang
Xingyu Pan
Jinpu Peng
Moudong Wu
Xiong Zhan
Wei Wang
Guohua Zhu
Nini An
Jun Pei
author_facet Shili Wang
Xingyu Pan
Jinpu Peng
Moudong Wu
Xiong Zhan
Wei Wang
Guohua Zhu
Nini An
Jun Pei
author_sort Shili Wang
collection DOAJ
description Background The study aims to investigate the role and significance of macrophage-related genes in peripheral blood during acute renal transplant rejection.Methods 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.Results 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.Conclusion 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.
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spelling doaj-art-a4bd692c91ce47ea86ad03d929c4ccb92025-08-20T02:48:53ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2532856CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejectionShili Wang0Xingyu Pan1Jinpu Peng2Moudong Wu3Xiong Zhan4Wei Wang5Guohua Zhu6Nini An7Jun Pei8Department of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaDepartment of Pediatric Urology, Guizhou Branch of Shanghai Children’s Medical Center Shanghai Jiaotong University School of Medicine, Guiyang, ChinaBackground The study aims to investigate the role and significance of macrophage-related genes in peripheral blood during acute renal transplant rejection.Methods 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.Results 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.Conclusion 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.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2532856Renal transplantationnoninvasiveacute rejectionmacrophagesimmune infiltration
spellingShingle Shili Wang
Xingyu Pan
Jinpu Peng
Moudong Wu
Xiong Zhan
Wei Wang
Guohua Zhu
Nini An
Jun Pei
CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
Renal Failure
Renal transplantation
noninvasive
acute rejection
macrophages
immune infiltration
title CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
title_full CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
title_fullStr CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
title_full_unstemmed CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
title_short CCR2 and TLR3: noninvasive macrophage-associated biomarkers of acute renal transplant rejection
title_sort ccr2 and tlr3 noninvasive macrophage associated biomarkers of acute renal transplant rejection
topic Renal transplantation
noninvasive
acute rejection
macrophages
immune infiltration
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2532856
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