ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1596364
This article is part of the Research TopicAdvancements in Immune Heterogeneity in Inflammatory Diseases and Cancer: New Targets, Mechanisms, and StrategiesView all 16 articles
Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis
Provisionally accepted
- Hebei University of Chinese Medicine, Shijiazhuang, Hebei Province, China
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Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by irreversible 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 using GEO datasets GSE242063 and GSE110147. 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 networks, and mRNA-miRNA/TF regulatory networks. Immune infiltration analyses, including the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA), were subsequently conducted.: 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.
Keywords: IPF (Idiopathic pulmonary fibrosis), hub genes, energy matebolism, GEO, DGE analysis
Received: 19 Mar 2025; Accepted: 04 Jun 2025.
Copyright: © 2025 Zhao, Sun, Liu, Huo, Liu, Wang and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shu Zhao, Hebei University of Chinese Medicine, Shijiazhuang, 050200, Hebei Province, China
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