Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy

Background: Energy metabolism and pyroptosis are integral to the pathogenesis of diabetic nephropathy (DN). However, the precise roles of energy metabolism and pyroptosis in DN development remain unclear. This study aims to elucidate the roles of energy metabolism- and pyroptosis-related differentia...

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Main Authors: Shan He, Jian Ye, Yu Wang, Lu yang Xie, Si Yi Liu, Qin kai Chen
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S240584402500581X
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author Shan He
Jian Ye
Yu Wang
Lu yang Xie
Si Yi Liu
Qin kai Chen
author_facet Shan He
Jian Ye
Yu Wang
Lu yang Xie
Si Yi Liu
Qin kai Chen
author_sort Shan He
collection DOAJ
description Background: Energy metabolism and pyroptosis are integral to the pathogenesis of diabetic nephropathy (DN). However, the precise roles of energy metabolism and pyroptosis in DN development remain unclear. This study aims to elucidate the roles of energy metabolism- and pyroptosis-related differentially expressed genes (EMAPRDEGs) in DN development. Methods: EMAPRDEGs were identified by querying the GeneCards and Gene Expression Omnibus (GEO) databases. Subsequent analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) network analysis. Additionally, mRNA-miRNA, mRNA-drug, and mRNA-transcription factor (TF) interaction networks were constructed. Differential expression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of EMAPRDEGs. Immune cell infiltration in DN was assessed using the ssGSEA algorithm, and the expression levels of EMAPRDEGs in DN tissues were validated by quantitative real-time PCR (qRT-PCR). Results: Thirteen EMAPRDEGs were identified, with GO and KEGG analyses indicating their involvement in energy metabolism pathways. GSEA revealed significant enrichment of these genes in biological pathways associated with diabetic nephropathy. PPI network analysis highlighted the central role of these genes within the relevant pathways. Predictive modeling demonstrated interactions between EMAPRDEGs, 69 miRNAs, and 117 TFs. Immune infiltration analysis showed substantial alterations in immune cell populations, with ADH1B and PC showing a significant correlation with natural killer cells and memory B cells. ROC curve analysis confirmed the diagnostic potential of EMAPRDEGs for diabetic nephropathy. qRT-PCR validated the expression patterns of CASP1, IL-18, PDK4, and FBP1, which were consistent with the bioinformatics predictions. Conclusion: Bioinformatics analysis identified 13 candidate EMAPRDEGs, among which CASP1, IL-18, PDK4, and FBP1 emerge as potential biomarkers for diabetic nephropathy.
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spelling doaj-art-b6d0454f7d29403194d12f2c4023f9042025-02-07T04:47:55ZengElsevierHeliyon2405-84402025-02-01113e42201Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathyShan He0Jian Ye1Yu Wang2Lu yang Xie3Si Yi Liu4Qin kai Chen5Department of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaCorresponding author.; Department of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaCorresponding author.; Department of Nephrology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaBackground: Energy metabolism and pyroptosis are integral to the pathogenesis of diabetic nephropathy (DN). However, the precise roles of energy metabolism and pyroptosis in DN development remain unclear. This study aims to elucidate the roles of energy metabolism- and pyroptosis-related differentially expressed genes (EMAPRDEGs) in DN development. Methods: EMAPRDEGs were identified by querying the GeneCards and Gene Expression Omnibus (GEO) databases. Subsequent analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Gene Set Enrichment Analysis (GSEA), and Protein-Protein Interaction (PPI) network analysis. Additionally, mRNA-miRNA, mRNA-drug, and mRNA-transcription factor (TF) interaction networks were constructed. Differential expression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of EMAPRDEGs. Immune cell infiltration in DN was assessed using the ssGSEA algorithm, and the expression levels of EMAPRDEGs in DN tissues were validated by quantitative real-time PCR (qRT-PCR). Results: Thirteen EMAPRDEGs were identified, with GO and KEGG analyses indicating their involvement in energy metabolism pathways. GSEA revealed significant enrichment of these genes in biological pathways associated with diabetic nephropathy. PPI network analysis highlighted the central role of these genes within the relevant pathways. Predictive modeling demonstrated interactions between EMAPRDEGs, 69 miRNAs, and 117 TFs. Immune infiltration analysis showed substantial alterations in immune cell populations, with ADH1B and PC showing a significant correlation with natural killer cells and memory B cells. ROC curve analysis confirmed the diagnostic potential of EMAPRDEGs for diabetic nephropathy. qRT-PCR validated the expression patterns of CASP1, IL-18, PDK4, and FBP1, which were consistent with the bioinformatics predictions. Conclusion: Bioinformatics analysis identified 13 candidate EMAPRDEGs, among which CASP1, IL-18, PDK4, and FBP1 emerge as potential biomarkers for diabetic nephropathy.http://www.sciencedirect.com/science/article/pii/S240584402500581XGEO databaseDiabetic nephropathyEnergy metabolism and pyroptosisBioinformaticsqRT-PCR
spellingShingle Shan He
Jian Ye
Yu Wang
Lu yang Xie
Si Yi Liu
Qin kai Chen
Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
Heliyon
GEO database
Diabetic nephropathy
Energy metabolism and pyroptosis
Bioinformatics
qRT-PCR
title Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
title_full Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
title_fullStr Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
title_full_unstemmed Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
title_short Identification and functional analysis of energy metabolism and pyroptosis-related genes in diabetic nephropathy
title_sort identification and functional analysis of energy metabolism and pyroptosis related genes in diabetic nephropathy
topic GEO database
Diabetic nephropathy
Energy metabolism and pyroptosis
Bioinformatics
qRT-PCR
url http://www.sciencedirect.com/science/article/pii/S240584402500581X
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