{ "abstract": "Idiopathic pulmonary fibrosis (IPF) is marked by aberrant lung remodeling and excessive extracellular matrix (ECM) accumulation. Previously, we observed elevated tryptophan (TRP) levels in the lungs of IPF patients, but its role in fibrogenesis remained unclear. This study examines whether TRP modulate the severity of lung fibrosis by measuring ECM component expression in TRP-treated lung fibroblasts. The activities of key TRP metabolism enzymes, tryptophan hydroxylase (TPH-1) and indoleamine 2,3-dioxygenase (IDO/TDO), were also assessed in IPF lung. Exogenous TRP administration in bleomycin-exposed mice significantly exacerbated lung damage and fibrosis. TPH-1 levels were elevated in lung tissues and primary fibroblasts of IPF patients compared to controls, while IDO/TDO expression showed no significant differences between two groups. TRP treatment increased fibroblast proliferation and upregulated collagen, fibronectin, and α-smooth muscle actin expression, whereas TRP deprivation reduced these ECM component levels. Additionally, TRP upregulated the AKT-mTORC1 and TGF-β1 signaling pathways in IPF fibroblasts. These findings indicate that elevated TRP levels contribute to IPF pathogenesis and suggest that targeting the TRP pathway could offer therapeutic potential for lung fibrosis including IPF.", "abstract_shown": true, "affiliations": [ "Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea", "Department of Pathology, Soonchunhyang University Bucheon Hospital, Gyeonggi-Do, South Korea", "Department of Internal Medicine Environmental Health Center, Kangwon National University, Chuncheon-si, Gangwon-do, South Korea" ], "article_type": "Research Article", "arxiv": null, "author_total": 15, "authors": [ { "affs": [ 0 ], "name": "Jisu Hong" }, { "affs": [ 0 ], "name": "Yunha Nam", "orcid": "0000-0003-3874-6089" }, { "affs": [ 0 ], "name": "Jib Yong Jung" }, { "affs": [ 0 ], "name": "Jun Yeong Baek" }, { "affs": [ 0 ], "name": "Eun Ji Park" }, { "affs": [ 0 ], "name": "Yemin Choi" }, { "affs": [ 0 ], "name": "Shinhee Park" }, { "affs": [ 0 ], "name": "Ae-Rin Baek" }, { "affs": [ 0 ], "name": "Hun-Gyu Hwang", "orcid": "0000-0001-9304-7219" }, { "affs": [ 0 ], "name": "Junehyuk Lee" }, { "affs": [ 0 ], "name": "An-Soo Jang" }, { "affs": [ 0 ], "name": "Do-Jin Kim" }, { "affs": [ 1 ], "name": "Su Sie Chin" }, { "affs": [ 2 ], "name": "Woo Jin Kim" }, { "affs": [ 0 ], "name": "Sung-Woo Park" } ], "bibtex": "https://research.draconitic.com/paper/e3ys5nf4jnjjy.bib", "cited_by": 0, "doi": "10.1371/journal.pone.0361463", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730385/", "id": "e3ys5nf4jnjjy", "issns": [ "1932-6203" ], "landing_url": "https://doi.org/10.1371/journal.pone.0361463", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Anatomy" ], [ "heading", "Animal Cells" ], [ "heading", "Biochemistry" ], [ "heading", "Biogenic Amines" ], [ "heading", "Biological Tissue" ], [ "heading", "Biology and Life Sciences" ], [ "heading", "Biology and life sciences" ], [ "heading", "Cell Biology" ], [ "heading", "Cell biology" ], [ "heading", "Cell signaling" ], [ "heading", "Cellular Types" ], [ "heading", "Collagens" ], [ "heading", "Connective Tissue" ], [ "heading", "Connective Tissue Cells" ], [ "heading", "Developmental Biology" ], [ "heading", "Fibroblasts" ], [ "heading", "Fibrosis" ], [ "heading", "Immunoblotting" ], [ "heading", "Medicine and Health Sciences" ], [ "heading", "Metabolic Pathways" ], [ "heading", "Metabolism" ], [ "heading", "Molecular Biology" ], [ "heading", "Molecular Biology Techniques" ], [ "heading", "Molecular Probe Techniques" ], [ "heading", "Neurochemistry" ], [ "heading", "Neuroscience" ], [ "heading", "Neurotransmitters" ], [ "heading", "Proteins" ], [ "heading", "Pulmonary Fibrosis" ], [ "heading", "Research Article" ], [ "heading", "Research and Analysis Methods" ], [ "heading", "Serotonin" ], [ "heading", "Signal transduction" ], [ "heading", "Signaling cascades" ], [ "heading", "TGF-beta signaling cascade" ], [ "plos", "/Biology and life sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Fibroblasts" ], [ "plos", "/Biology and life sciences/Biochemistry/Metabolism/Metabolic pathways" ], [ "plos", "/Biology and life sciences/Biochemistry/Neurochemistry/Neurotransmitters/Biogenic amines/Serotonin" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Amino acids/Aromatic amino acids/Tryptophan" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Collagens" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Connective tissue cells/Fibroblasts" ], [ "plos", "/Biology and life sciences/Developmental biology/Fibrosis" ], [ "plos", "/Biology and life sciences/Developmental biology/Fibrosis/Pulmonary fibrosis" ], [ "plos", "/Biology and life sciences/Molecular biology/Molecular biology techniques/Molecular probe techniques/Immunoblotting" ], [ "plos", "/Biology and life sciences/Neuroscience/Neurochemistry/Neurotransmitters/Biogenic amines/Serotonin" ], [ "plos", "/Medicine and health sciences/Anatomy/Biological tissue/Connective tissue/Connective tissue cells/Fibroblasts" ], [ "plos", "/Physical sciences/Chemistry/Chemical compounds/Organic compounds/Amino acids/Aromatic amino acids/Tryptophan" ], [ "plos", "/Physical sciences/Chemistry/Organic chemistry/Organic compounds/Amino acids/Aromatic amino acids/Tryptophan" ], [ "plos", "/Research and analysis methods/Molecular biology techniques/Molecular probe techniques/Immunoblotting" ] ], "openalex": null, "pdf_url": null, "pmcid": "PMC13730385", "pmid": "42976151", "published": "2026-11-03", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/e3ys5nf4jnjjy.ris", "sources": [ { "first_seen": "2026-11-04T12:20:43Z", "native_id": "10.1371/journal.pone.0361463", "source": "plos", "url": "https://doi.org/10.1371/journal.pone.0361463" }, { "first_seen": "2026-11-07T12:22:57Z", "native_id": "PMC13730385", "source": "pmc", "url": "https://doi.org/10.1371/journal.pone.0361463" } ], "subjects": [ { "field": "biochemistry", "origin": "plos:metabolism", "subfield": "enzymology-metabolism" }, { "field": "biochemistry", "origin": "heading:Molecular Biology", "subfield": "molecular-biology" }, { "field": "biology", "origin": "heading:Cell Biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:developmental biology", "subfield": "developmental-biology" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "Exogenous tryptophan aggravates experimental lung fibrosis through activation of AKT-mTORC1 pathway", "title_text": "Exogenous tryptophan aggravates experimental lung fibrosis through activation of AKT-mTORC1 pathway", "type": "peer-reviewed", "updated_at": "2026-11-07T12:22:57Z", "url": "https://research.draconitic.com/paper/e3ys5nf4jnjjy", "venue": "PLOS One", "versions": [] }