{ "abstract": "Background: 5-Hydroxymethylfurfural (5-HMF), a ubiquitous furan derivative formed during the thermal processing of carbohydrate-rich foods, represents a widespread dietary exposure. However, its potential contribution to idiopathic pulmonary fibrosis (IPF) remains unclear. This study investigated the molecular links between 5-HMF and IPF using an integrated computational and experimental approach. Methods: IPF-related genes were identified through transcriptomic analysis combining differential expression analysis and weighted gene co-expression network analysis. Candidate targets were obtained by intersecting IPF-associated genes with predicted 5-HMF targets. Functional enrichment analysis, ensemble machine learning, and SHAP interpretation were performed to prioritize candidate targets, while molecular docking was used to explore potential 5-HMF–target interactions. A bleomycin-induced mouse model of pulmonary fibrosis was further used to evaluate the effects of 5-HMF on fibrotic lung injury and the transcriptional expression of prioritized candidate genes. Results: A total of 1,776 IPF-associated genes and 143 predicted 5-HMF targets were identified, yielding 12 overlapping candidate targets. Enrichment analysis implicated these genes in fibrosis-related pathways, including chemical carcinogenesis–receptor activation and estrogen signaling. Machine learning analysis prioritized seven core targets (CA2, CA4, ESR2, F10, HSP90AA1, PLA2G1B, and PTPRB), all of which accommodated 5-HMF in their orthosteric pockets in blind docking, albeit with weak, non-selective Vina scores (−4.5 to −5.4 kcal/mol). In vivo, 5-HMF significantly exacerbated bleomycin-induced pulmonary fibrosis, as demonstrated by aggravated lung injury, increased collagen deposition, and elevated expression of Hsp90aa1, Pla2g1b, Ca4, F10, Acta2, and Col1a1. Conclusion: Our findings suggest that 5-HMF may exacerbate fibrotic lung injury through multiple fibrosis-related molecular targets and pathways. These findings provide preliminary evidence for a potential association between 5-HMF exposure and the aggravation of pulmonary fibrosis, while further studies are required to determine whether 5-HMF can independently initiate fibrotic pathology.", "abstract_shown": true, "affiliations": [ "Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.", "Department of Respiratory Disease, Chongqing Jiulongpo Science City People's Hospital, Chongqing, China." ], "article_type": "Research Article", "arxiv": null, "author_total": 4, "authors": [ { "affs": [ 0 ], "name": "Qinghuan Yang" }, { "affs": [ 1 ], "name": "Fuli Li" }, { "affs": [ 0 ], "name": "Jiani Li" }, { "affs": [ 1 ], "name": "Ting Qin", "orcid": "0009-0000-3006-3676" } ], "bibtex": "https://research.draconitic.com/paper/b08p8fmf8qwbg.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0361700", "fulltext_url": "https://europepmc.org/articles/PMC13727047", "id": "b08p8fmf8qwbg", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0361700", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Algorithms" ], [ "heading", "Animal Models" ], [ "heading", "Animal Studies" ], [ "heading", "Applied Mathematics" ], [ "heading", "Artificial Intelligence" ], [ "heading", "Biology and Life Sciences" ], [ "heading", "Chemistry" ], [ "heading", "Computational Chemistry" ], [ "heading", "Computer and Information Sciences" ], [ "heading", "Developmental Biology" ], [ "heading", "Diet" ], [ "heading", "Experimental Organism Systems" ], [ "heading", "Fibrosis" ], [ "heading", "Gene Expression" ], [ "heading", "Genetics" ], [ "heading", "Machine Learning" ], [ "heading", "Machine Learning Algorithms" ], [ "heading", "Mathematics" ], [ "heading", "Medicine and Health Sciences" ], [ "heading", "Model Organisms" ], [ "heading", "Molecular Docking" ], [ "heading", "Mouse Models" ], [ "heading", "Nutrition" ], [ "heading", "Pathology and Laboratory Medicine" ], [ "heading", "Physical Sciences" ], [ "heading", "Pulmonary Fibrosis" ], [ "heading", "Research Article" ], [ "heading", "Research and Analysis Methods" ], [ "heading", "Simulation and Modeling" ], [ "heading", "Toxicology" ], [ "openalex", "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis" ], [ "plos", "/Biology and life sciences/Developmental biology/Fibrosis/Pulmonary fibrosis" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression" ], [ "plos", "/Biology and life sciences/Nutrition/Diet" ], [ "plos", "/Biology and life sciences/Toxicology" ], [ "plos", "/Computer and information sciences/Artificial intelligence/Machine learning" ], [ "plos", "/Computer and information sciences/Artificial intelligence/Machine learning/Machine learning algorithms" ], [ "plos", "/Medicine and health sciences/Nutrition/Diet" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology" ], [ "plos", "/Physical sciences/Chemistry/Computational chemistry/Molecular docking" ], [ "plos", "/Physical sciences/Mathematics/Applied mathematics/Algorithms/Machine learning algorithms" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models" ], [ "plos", "/Research and analysis methods/Model organisms/Mouse models" ], [ "plos", "/Research and analysis methods/Simulation and modeling/Algorithms/Machine learning algorithms" ] ], "openalex": "W7225129581", "pdf_url": "https://europepmc.org/articles/PMC13727047?pdf=render", "pmcid": "PMC13727047", "pmid": "42970606", "published": "2026-11-02", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/b08p8fmf8qwbg.ris", "sources": [ { "first_seen": "2026-11-03T12:20:16Z", "native_id": "10.1371/journal.pone.0361700", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0361700" }, { "first_seen": "2026-11-04T15:20:43Z", "native_id": "MED:42970606", "source": "europepmc", "url": "https://europepmc.org/article/MED/42970606" }, { "first_seen": "2026-11-05T12:23:15Z", "native_id": "PMC13727047", "source": "pmc", "url": "https://doi.org/10.1371/journal.pone.0361700" } ], "subjects": [ { "field": "biochemistry", "origin": "heading:Gene Expression", "subfield": "molecular-biology" }, { "field": "biology", "origin": "plos:developmental biology", "subfield": "developmental-biology" }, { "field": "chemistry", "origin": "heading:Computational Chemistry", "subfield": "theoretical" }, { "field": "medicine", "origin": "plos:nutrition", "subfield": "nutrition" }, { "field": "medicine", "origin": "plos:toxicology", "subfield": "pharmacology-toxicology" } ], "title": "Integrative network toxicology and machine learning reveal the potential role of 5-hydroxymethylfurfural in exacerbating pulmonary fibrosis", "title_text": "Integrative network toxicology and machine learning reveal the potential role of 5-hydroxymethylfurfural in exacerbating pulmonary fibrosis", "type": "peer-reviewed", "updated_at": "2026-11-06T12:22:51Z", "url": "https://research.draconitic.com/paper/b08p8fmf8qwbg", "venue": "PLOS One", "versions": [] }