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Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA

Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between...

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Autores principales: Wei, Jinshuang, Zhang, Junlin, Wei, Junyu, Hu, Miaoyue, Chen, Xiuqi, Qin, Xuankai, Chen, Jie, Lei, Fengying, Qin, Yuanhan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897545/
https://www.ncbi.nlm.nih.gov/pubmed/36735737
http://dx.doi.org/10.1371/journal.pone.0281439
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author Wei, Jinshuang
Zhang, Junlin
Wei, Junyu
Hu, Miaoyue
Chen, Xiuqi
Qin, Xuankai
Chen, Jie
Lei, Fengying
Qin, Yuanhan
author_facet Wei, Jinshuang
Zhang, Junlin
Wei, Junyu
Hu, Miaoyue
Chen, Xiuqi
Qin, Xuankai
Chen, Jie
Lei, Fengying
Qin, Yuanhan
author_sort Wei, Jinshuang
collection PubMed
description Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between several gene sets and phenotypes. We screened potential target genes related to AKI through WGCNA to provide a reference for the diagnosis and treatment of AKI. Key biomolecules of AKI were investigated based on transcriptome analysis. RNA sequencing data from 39 kidney biopsy specimens of AKI patients and 9 normal subjects were downloaded from the GEO database. By WGCNA, the top 20% of mRNAs with the largest variance in the data matrix were used to construct a gene co-expression network with a p-value < 0.01 as a screening condition, showing that the blue module was most closely associated with AKI. Thirty-two candidate biomarker genes were screened according to the threshold values of |MM|≥0.86 and |GS|≥0.4, and PPI and enrichment analyses were performed. The top three genes with the most connected nodes, alanine—glyoxylate aminotransferase 2(AGXT2), serine hydroxymethyltransferase 1(SHMT1) and aconitase 2(ACO2), were selected as the central genes based on the PPI network. A rat AKI model was constructed, and the mRNA and protein expression levels of the central genes in the model and control groups were verified by PCR and immunohistochemistry experiments. The results showed that the relative mRNA expression and protein levels of AGXT2, SHMT1 and ACO2 showed a decrease in the model group. In conclusion, we inferred that there is a close association between AGXT2, SHMT1 and ACO2 genes and the development of AKI, and the down-regulation of their expression levels may induce AKI.
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spelling pubmed-98975452023-02-04 Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA Wei, Jinshuang Zhang, Junlin Wei, Junyu Hu, Miaoyue Chen, Xiuqi Qin, Xuankai Chen, Jie Lei, Fengying Qin, Yuanhan PLoS One Research Article Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between several gene sets and phenotypes. We screened potential target genes related to AKI through WGCNA to provide a reference for the diagnosis and treatment of AKI. Key biomolecules of AKI were investigated based on transcriptome analysis. RNA sequencing data from 39 kidney biopsy specimens of AKI patients and 9 normal subjects were downloaded from the GEO database. By WGCNA, the top 20% of mRNAs with the largest variance in the data matrix were used to construct a gene co-expression network with a p-value < 0.01 as a screening condition, showing that the blue module was most closely associated with AKI. Thirty-two candidate biomarker genes were screened according to the threshold values of |MM|≥0.86 and |GS|≥0.4, and PPI and enrichment analyses were performed. The top three genes with the most connected nodes, alanine—glyoxylate aminotransferase 2(AGXT2), serine hydroxymethyltransferase 1(SHMT1) and aconitase 2(ACO2), were selected as the central genes based on the PPI network. A rat AKI model was constructed, and the mRNA and protein expression levels of the central genes in the model and control groups were verified by PCR and immunohistochemistry experiments. The results showed that the relative mRNA expression and protein levels of AGXT2, SHMT1 and ACO2 showed a decrease in the model group. In conclusion, we inferred that there is a close association between AGXT2, SHMT1 and ACO2 genes and the development of AKI, and the down-regulation of their expression levels may induce AKI. Public Library of Science 2023-02-03 /pmc/articles/PMC9897545/ /pubmed/36735737 http://dx.doi.org/10.1371/journal.pone.0281439 Text en © 2023 Wei et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wei, Jinshuang
Zhang, Junlin
Wei, Junyu
Hu, Miaoyue
Chen, Xiuqi
Qin, Xuankai
Chen, Jie
Lei, Fengying
Qin, Yuanhan
Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title_full Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title_fullStr Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title_full_unstemmed Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title_short Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA
title_sort identification of agxt2, shmt1, and aco2 as important biomarkers of acute kidney injury by wgcna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897545/
https://www.ncbi.nlm.nih.gov/pubmed/36735737
http://dx.doi.org/10.1371/journal.pone.0281439
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