ArticleJournal of advanced research2025
Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- IFN-γ-Associated Signaling Networks in Interstitial Lung Disease Associated With Sjögren's Disease.Immunity, inflammation and disease · 2026Review
- Cell-Specific Modulation of the Aryl Hydrocarbon Receptor by Kynurenine in Pulmonary Fibrosis Requires Microenvironmental Crosstalk.bioRxiv : the preprint server for biology · 2026Article
- Discovery of biomarkers for primary Sj ögren's syndrome based on multi-omics data, construction of diagnostic models, and clinical correlation analysis.Arthritis research & therapy · 2026Article
- Kynurenine-AhR-SLC39A10-ZnCell communication and signaling : CCS · 2026Article
- Construction of Rheumatoid Arthritis-Associated Interstitial Lung Disease diagnostic model and identification of biomarkers based on a multi-omics integration strategy of machine learning.Clinics (Sao Paulo, Brazil) · 2026Article
- Tryptophan metabolism reprogramming regulates Th1/Th2 immune balance and inhibits mast cell activation.Amino acids · 2026Article
- Clinical features, diagnosis, and treatment of primary Sjögren's disease with interstitial lung disease: A narrative review.Frontiers in immunology · 2026Review
- Curcumin in Fibrosis Treatment: A Review.Drug design, development and therapy · 2026Review
- BRPF1 inhibitor GSK6853 inhibits NSCLC cell proliferation via the JAK2/STAT3/CCNA2 axis to induce cell cycle arrest.Investigational new drugs · 2025Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- SIK2 Drives Pulmonary Fibrosis by Enhancing Fibroblast Glycolysis and Activation.Biomedicines · 2025Article
- Metabolomic profiling reveals unique markers for Pseudomonas aeruginosa LasR deficiency.Scientific reports · 2025Article
- [Therapeutic mechanism ofNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- circ0066187 promotes pulmonary fibrogenesis through targeting STAT3-mediated metabolism signal pathway.Cellular and molecular life sciences : CMLS · 2025Article
- CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.JCI insight · 2025Article
- IL-27 Modulates Mesenchymal Stem Cell Immunoplasticity for Enhanced Lupus Nephritis Therapy via the JAK1-STAT1-IDO Axis and Tryptophan Metabolic Orchestration.Research (Washington, D.C.) · 2025Article
- Heliox preconditioning exerts pulmonary protection effects on neonatal acute respiratory distress syndrome by inhibiting oxidative stress and apoptosis.Frontiers in pharmacology · 2025Article
- Review
- Advances in the pharmacological mechanisms of berberine in the treatment of fibrosis.Frontiers in pharmacology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPulmonary fibrosis (PF) is a fatal fibrotic lung disease without any options to halt disease progression. Feasible evidence suggests that aberrant metabolism of amino acids may play a role in the pathoetiology of PF. However, the exact impact of kynurenine (Kyn), a metabolite derived from tryptophan (Trp) on PF is yet to be addressed.
objectivesThis study aims to elucidate the role of kynurenine in both the onset and advancement of PF.
methodsLiquid chromatography-tandem mass spectrometry was employed to assess Kyn levels in patients with idiopathic PF and PF associated with Sjögren's syndrome. Additionally, a mouse model of PF induced by bleomycin was utilized to study the impact of Kyn administration. Furthermore, cell models treated with TGF-β1 were used to explore the mechanism by which Kyn inhibits fibroblast functions.
resultsWe demonstrated that high levels of Kyn are a clinical feature in both idiopathic PF patients and primary Sjögren syndrome associated PF patients. Further studies illustrated that Kyn served as a braking molecule to suppress fibroblast functionality, thereby protecting mice from bleomycin-induced lung fibrosis. The protective effects depend on AHR, in which Kyn induces AHR nuclear translocation, where it upregulates PTEN expression to blunt TGF-β mediated AKT/mTOR signaling in fibroblasts. However, in fibrotic microenviroment, the expression of AHR is repressed by methyl-CpG-binding domain 2 (MBD2), a reader interpreting the effect of DNA methylation, which results in a significantly reduced sensitivity of Kyn to fibroblasts. Therefore, exogenous administration of Kyn substantially reversed established PF.
conclusionOur studies not only highlighted a critical role of Trp metabolism in PF pathogenesis, but also provided compelling evidence suggesting that Kyn could serve as a promising metabolite against PF.
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