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

He, Sheng; McClements, David Julian; Yan, Fangran; Li, Junda; Liao, Xueming; Ling, Maoyao; Ren, Jing; Pan, Linghui

doi:10.3389/fphys.2022.951855

Cited by 9 publications

(4 citation statements)

References 78 publications

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“…Regarding CC, Mitophagy-DEGs were predominantly associated with the myelin sheath, ribosome, autophagosome, cytosolic ribosome, and autophagosome. Regarding MF, mitophagy-DEGs exhibited signi cant enrichments in ubiquitin-like protein ligase binding, ubiquitin protein ligase binding [22], ATP hydrolysis activity, and p53 binding. The KEGG pathway analysis revealed signi cant enrichments in mitophagy-animal, HIF-1 signaling pathway, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway (Fig.…”

Section: Validation and Enrichment Analysis Of Mitophagy-degsmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

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Background: Myocardial ischemia is a prevalent cardiovascular disease with a high incidence and mortality rate. Restoring blood flow to the ischemic myocardium as soon as possible is crucial for improving patients' prognosis, but this process can lead to myocardial ischemia-reperfusion injury (MIRI). Mitophagy is a specific cellular autophagic process that has been consistently linked to various cardiovascular disorders.Nevertheless, the connection between ischemia-reperfusion and mitophagy remains unclear. This study's objective is to discern and substantiate central mitophagy-related genes associated with MIRI through bioinformatics analysis. Methods: The microarray expression profile dataset (GSE108940) was obtained from the Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using GEO2R. These DEGs were then cross-referenced with genes in the mitophagy database. Differential nucleotide sequence analysis used enrichment analysis.The DEGs were obtained through protein-protein interaction (PPI)network analysis. And the hub genes were clustered by cytoHubba and MCODE of Cytoscape software. GSEA analysis was conducted on central genes. Finally, we conducted Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses to corroborate the expression patterns of pivotal genes in MIRI-afflicted rats. Results: 2719 DEGs and 61 mitophagy-DEGs were obtained,followed by enrichment analyses and construction of PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1,HIF-1α and BNIP3 were the 7 hub genes identified by cytoHubba and MCODE of Cytoscape software. The functional clustering score of HIF-1α and BNIP3 was 9.647 by analysis of Cytoscape (MCODE). In our constructed MIRI rat model, western blot and immunofluorescence confirmed a significant elevation in the expression of HIF-1α and BNIP3, along with a significant increase in the ratio of LC3II to LC3I. Finally,qPCR confirmed that expression of HIF-1α, BNIP3 and LC3 mRNA in MIRI group was elevated significantly. Conclusions: Seven central genes among the mitophagy-related DEGs have been pinpointed, potentially holding pivotal significance in MIRI, which indicated that HIF-1α/BNIP3 pathway of mitophag was correlated with pathogenesis of MIRI. Mitophagy may play an important role in MIRI.This research will offer valuable insights into the underlying mechanisms and potential therapeutic targets, which can be explored in future studies.

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Section: Validation and Enrichment Analysis Of Mitophagy-degsmentioning

confidence: 99%

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

Chen,

Liu,

Yuan

et al. 2023

Preprint

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“…Further GO and KEGG pathway enrichment analyses suggested that these CRs were involved in cell cycles, p38 MAPK, p53, FoxO, and NF-κB signaling pathways. Recently, two bioinformatic studies have been published in which renal IRI biomarkers were enriched in the MAPK pathway [41,42]. Although these bioinformatical data were derived from animal experiments, they were in line with our findings from human renal IRI and further confirmed the importance of CRs and the MAPK pathway in renal IRI.…”

Section: Discussionsupporting

confidence: 87%

GADD45A and GADD45B as Novel Biomarkers Associated with Chromatin Regulators in Renal Ischemia-Reperfusion Injury

Xie

Huang

et al. 2023

IJMS

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Chromatin regulators (CRs) are essential upstream regulatory factors of epigenetic modification. The role of CRs in the pathogenesis of renal ischemia-reperfusion injury (IRI) remains unclear. We analyzed a bioinformatic analysis on the differentially expressed chromatin regulator genes in renal IRI patients using data from public domains. The hub CRs identified were used to develop a risk prediction model for renal IRI, and their expressions were also validated using Western blot, qRT-PCR, and immunohistochemistry in a murine renal IRI model. We also examined the relationships between hub CRs and infiltrating immune cells in renal IRI and used network analysis to explore drugs that target hub CRs and their relevant downstream microRNAs. The results of machine learning methods showed that five genes (DUSP1, GADD45A, GADD45B, GADD45G, HSPA1A) were upregulated in renal IRI, with key roles in the cell cycle, p38 MAPK signaling pathway, p53 signaling pathway, FoxO signaling pathway, and NF-κB signaling pathway. Two genes from the network, GADD45A and GADD45B (growth arrest and DNA damage-inducible protein 45 alpha and beta), were chosen for the renal IRI risk prediction model. They all showed good performance in the testing and validation cohorts. Mice with renal IRI showed significantly upregulated GADD45A and GADD45B expression within kidneys compared to sham-operated mice. GADD45A and GADD45B showed correlations with plasmacytoid dendritic cells (pDCs) in infiltrating immune cell analysis and enrichment in the MAPK pathway based on the weighted gene co-expression network analysis (WGCNA) method. Candidate drugs that target GADD45A and GADD45B include beta-escin, sertraline, primaquine, pimozide, and azacyclonol. The dysregulation of GADD45A and GADD45B is related to renal IRI and the infiltration of pDCs, and drugs that target GADD45A and GADD45B may have therapeutic potential for renal IRI.

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“…Regarding CC, Mitophagy-DEGs were predominantly associated with the myelin sheath, ribosome, autophagosome, cytosolic ribosome, and autophagosome. Regarding MF, mitophagy-DEGs exhibited significant enrichments in ubiquitin-like protein ligase binding, ubiquitin protein ligase binding [ 23 ], ATP hydrolysis activity, and p53 binding. The KEGG pathway analysis revealed significant enrichments in mitophagy-animal, HIF-1 signaling pathway, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway (Fig.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

Chen,

Liu,

Yuan

et al. 2024

BMC Cardiovasc Disord

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Background Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia–reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia–reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis. Methods We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein–protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes. Results A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes. Conclusions This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.

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

Cited by 9 publications

References 78 publications

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

WITHDRAWN: Integrated bioinformatics identify the critical genes of mitophagy in myocardial ischemia- reperfusion injury

GADD45A and GADD45B as Novel Biomarkers Associated with Chromatin Regulators in Renal Ischemia-Reperfusion Injury

Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury

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