Identification of diagnostic hub genes related to energy metabolism in idiopathic pulmonary fibrosis.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-06-26 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1596364

S Zhao, B C Sun, N Liu, R Huo, L S Liu, J P Wang, C Y Fang

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引用次数: 0

Abstract

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.

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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。

背景：特发性肺纤维化（IPF）是一种慢性进行性肺部疾病，随着时间的推移而恶化，最终导致呼吸衰竭。新出现的证据表明，在IPF发病过程中，能量代谢失调驱动成纤维细胞活化和细胞外基质重塑。为了系统地研究代谢重编程机制，我们对能量代谢相关的差异表达基因（EMRDEGs）及其在纤维化重塑中的调控网络进行了综合生物信息学分析。方法：通过访问GEO数据库的GSE242063和GSE110147数据集对差异表达基因（differential expression Genes, DEGs）进行鉴定。从GeneCards中提取能量代谢相关基因（EMRGs），通过维恩图分析获得EMRGs。随后的分析包括功能富集（GO/KEGG）、蛋白-蛋白相互作用网络、mRNA-miRNA、mrna -转录因子相互作用网络。随后进行免疫浸润分析，包括CIBERSORT算法和单样本基因集富集分析（ssGSEA）。结果：我们鉴定出12个emrdeg和8个枢纽基因（ACSL1、CEBPD、CFH、HMGCS1、IL6、SOCS3、TLR2和UCP2）。调控网络分析显示，HMGCS1是一个新的ipf相关基因，与PPARα信号相互作用，而SOCS3通过foxa1 /2介导的转录调控和JAK/STAT3通路抑制，协调多个枢纽基因（IL6、CEBPD、UCP2和CFH）。免疫谱显示了中心基因与免疫细胞的显著相关性，特别是中性粒细胞介导的差异基因表达和微环境重塑。结论：核心emrdeg （HMGCS1和SOCS3）和优先通路（PPARα信号、FOXA网络、JAK/STAT3抑制）阐明了纤维化进展中的代谢重编程机制。这些分子特征为IPF的诊断提供了新的临床生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

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.