Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice

Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia–reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia–reperfusion...

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Main Authors: Sheng He, Lili He, Fangran Yan, Junda Li, Xiaoting Liao, Maoyao Ling, Ren Jing, Linghui Pan
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.951855/full
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author Sheng He
Sheng He
Sheng He
Sheng He
Sheng He
Lili He
Fangran Yan
Junda Li
Xiaoting Liao
Maoyao Ling
Ren Jing
Linghui Pan
Linghui Pan
Linghui Pan
Linghui Pan
author_facet Sheng He
Sheng He
Sheng He
Sheng He
Sheng He
Lili He
Fangran Yan
Junda Li
Xiaoting Liao
Maoyao Ling
Ren Jing
Linghui Pan
Linghui Pan
Linghui Pan
Linghui Pan
author_sort Sheng He
collection DOAJ
description Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia–reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia–reperfusion injury (IRI-AKI).Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)–hub gene and miRNA–hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb.Result: A total of 323 common differentially expressed genes were identified in the renal ischemia–reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein–Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes.Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia–reperfusion injury–acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia–reperfusion injury–acute kidney injury.
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spelling doaj.art-371231f1970b4702b2eb5ca8df6a30ab2022-12-22T03:21:55ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.951855951855Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in miceSheng He0Sheng He1Sheng He2Sheng He3Sheng He4Lili He5Fangran Yan6Junda Li7Xiaoting Liao8Maoyao Ling9Ren Jing10Linghui Pan11Linghui Pan12Linghui Pan13Linghui Pan14Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaGuangxi Engineering Research Center for Tissue and Organ Injury and Repair Medicine, Nanning, ChinaGuangxi Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, ChinaGuangxi Clinical Research Center for Anesthesiology, Nanning, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Southern China University, Hengyang, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Southern China University, Hengyang, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, ChinaGuangxi Engineering Research Center for Tissue and Organ Injury and Repair Medicine, Nanning, ChinaGuangxi Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Nanning, ChinaGuangxi Clinical Research Center for Anesthesiology, Nanning, ChinaBackground: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia–reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia–reperfusion injury (IRI-AKI).Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)–hub gene and miRNA–hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb.Result: A total of 323 common differentially expressed genes were identified in the renal ischemia–reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein–Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes.Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia–reperfusion injury–acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia–reperfusion injury–acute kidney injury.https://www.frontiersin.org/articles/10.3389/fphys.2022.951855/fullacute kidney injuryischemia reperfusionhub genesStat3MYC
spellingShingle Sheng He
Sheng He
Sheng He
Sheng He
Sheng He
Lili He
Fangran Yan
Junda Li
Xiaoting Liao
Maoyao Ling
Ren Jing
Linghui Pan
Linghui Pan
Linghui Pan
Linghui Pan
Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
Frontiers in Physiology
acute kidney injury
ischemia reperfusion
hub genes
Stat3
MYC
title Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
title_full Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
title_fullStr Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
title_full_unstemmed Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
title_short Identification of hub genes associated with acute kidney injury induced by renal ischemia–reperfusion injury in mice
title_sort identification of hub genes associated with acute kidney injury induced by renal ischemia reperfusion injury in mice
topic acute kidney injury
ischemia reperfusion
hub genes
Stat3
MYC
url https://www.frontiersin.org/articles/10.3389/fphys.2022.951855/full
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