S Zhao, B C Sun, N Liu, R Huo, L S Liu, J P Wang, C Y Fang
{"title":"特发性肺纤维化中与能量代谢相关的诊断中枢基因的鉴定。","authors":"S Zhao, B C Sun, N Liu, R Huo, L S Liu, J P Wang, C Y Fang","doi":"10.3389/fmolb.2025.1596364","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that worsens over time, culminating in respiratory failure. Emerging evidence implicates dysregulated energy metabolism in driving fibroblast activation and extracellular matrix remodeling during IPF pathogenesis. To systematically investigate metabolic reprogramming mechanisms, we performed integrated bioinformatics analyses focusing on energy metabolism-related differentially expressed genes (EMRDEGs) and their regulatory networks in fibrotic remodeling.</p><p><strong>Methods: </strong>Differentially Expressed Genes (DEGs) were identified by accessing datasets GSE242063 and GSE110147 from the GEO database. Energy metabolism-related genes (EMRGs) were extracted from GeneCards, followed by Venn diagram analysis to obtain EMRDEGs. Subsequent analyses included functional enrichment (GO/KEGG), protein-protein interaction network, and mRNA-miRNA, mRNA-transcription factor interaction networks. Immune infiltration analyses, including the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA), were subsequently conducted.</p><p><strong>Results: </strong>We identified 12 EMRDEGs and eight hub genes (<i>ACSL1</i>, <i>CEBPD</i>, <i>CFH</i>, <i>HMGCS1</i>, <i>IL6</i>, <i>SOCS3</i>, <i>TLR2</i>, and <i>UCP2</i>). Regulatory network analysis revealed <i>HMGCS1</i> as a novel IPF-associated gene interacting with PPARα signaling, while <i>SOCS3</i> coordinated multiple hub genes (<i>IL6</i>, <i>CEBPD</i>, <i>UCP2</i>, and <i>CFH</i>) through FOXA1/2-mediated transcriptional regulation alongside JAK/STAT3 pathway suppression. Immune profiling demonstrated significant hub gene-immune cell correlations, particularly neutrophil-mediated differential gene expression and microenvironment remodeling.</p><p><strong>Conclusion: </strong>The core EMRDEGs (<i>HMGCS1</i> and <i>SOCS3</i>) and prioritized pathways (PPARα signaling, FOXA networks, JAK/STAT3 suppression) elucidate metabolic reprogramming mechanisms in fibrotic progression. These molecular signatures provide novel clinical biomarkers for IPF diagnosis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1596364"},"PeriodicalIF":3.9000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241802/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis.\",\"authors\":\"S Zhao, B C Sun, N Liu, R Huo, L S Liu, J P Wang, C Y Fang\",\"doi\":\"10.3389/fmolb.2025.1596364\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that worsens over time, culminating in respiratory failure. Emerging evidence implicates dysregulated energy metabolism in driving fibroblast activation and extracellular matrix remodeling during IPF pathogenesis. To systematically investigate metabolic reprogramming mechanisms, we performed integrated bioinformatics analyses focusing on energy metabolism-related differentially expressed genes (EMRDEGs) and their regulatory networks in fibrotic remodeling.</p><p><strong>Methods: </strong>Differentially Expressed Genes (DEGs) were identified by accessing datasets GSE242063 and GSE110147 from the GEO database. Energy metabolism-related genes (EMRGs) were extracted from GeneCards, followed by Venn diagram analysis to obtain EMRDEGs. Subsequent analyses included functional enrichment (GO/KEGG), protein-protein interaction network, and mRNA-miRNA, mRNA-transcription factor interaction networks. Immune infiltration analyses, including the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA), were subsequently conducted.</p><p><strong>Results: </strong>We identified 12 EMRDEGs and eight hub genes (<i>ACSL1</i>, <i>CEBPD</i>, <i>CFH</i>, <i>HMGCS1</i>, <i>IL6</i>, <i>SOCS3</i>, <i>TLR2</i>, and <i>UCP2</i>). Regulatory network analysis revealed <i>HMGCS1</i> as a novel IPF-associated gene interacting with PPARα signaling, while <i>SOCS3</i> coordinated multiple hub genes (<i>IL6</i>, <i>CEBPD</i>, <i>UCP2</i>, and <i>CFH</i>) through FOXA1/2-mediated transcriptional regulation alongside JAK/STAT3 pathway suppression. Immune profiling demonstrated significant hub gene-immune cell correlations, particularly neutrophil-mediated differential gene expression and microenvironment remodeling.</p><p><strong>Conclusion: </strong>The core EMRDEGs (<i>HMGCS1</i> and <i>SOCS3</i>) and prioritized pathways (PPARα signaling, FOXA networks, JAK/STAT3 suppression) elucidate metabolic reprogramming mechanisms in fibrotic progression. These molecular signatures provide novel clinical biomarkers for IPF diagnosis.</p>\",\"PeriodicalId\":12465,\"journal\":{\"name\":\"Frontiers in Molecular Biosciences\",\"volume\":\"12 \",\"pages\":\"1596364\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-06-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241802/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Biosciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3389/fmolb.2025.1596364\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2025.1596364","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis.
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease that worsens over time, culminating in respiratory failure. Emerging evidence implicates dysregulated energy metabolism in driving fibroblast activation and extracellular matrix remodeling during IPF pathogenesis. To systematically investigate metabolic reprogramming mechanisms, we performed integrated bioinformatics analyses focusing on energy metabolism-related differentially expressed genes (EMRDEGs) and their regulatory networks in fibrotic remodeling.
Methods: Differentially Expressed Genes (DEGs) were identified by accessing datasets GSE242063 and GSE110147 from the GEO database. Energy metabolism-related genes (EMRGs) were extracted from GeneCards, followed by Venn diagram analysis to obtain EMRDEGs. Subsequent analyses included functional enrichment (GO/KEGG), protein-protein interaction network, and mRNA-miRNA, mRNA-transcription factor interaction networks. Immune infiltration analyses, including the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA), were subsequently conducted.
Results: We identified 12 EMRDEGs and eight hub genes (ACSL1, CEBPD, CFH, HMGCS1, IL6, SOCS3, TLR2, and UCP2). Regulatory network analysis revealed HMGCS1 as a novel IPF-associated gene interacting with PPARα signaling, while SOCS3 coordinated multiple hub genes (IL6, CEBPD, UCP2, and CFH) through FOXA1/2-mediated transcriptional regulation alongside JAK/STAT3 pathway suppression. Immune profiling demonstrated significant hub gene-immune cell correlations, particularly neutrophil-mediated differential gene expression and microenvironment remodeling.
Conclusion: The core EMRDEGs (HMGCS1 and SOCS3) and prioritized pathways (PPARα signaling, FOXA networks, JAK/STAT3 suppression) elucidate metabolic reprogramming mechanisms in fibrotic progression. These molecular signatures provide novel clinical biomarkers for IPF diagnosis.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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