ArticleThe American journal of pathology2011
The aryl hydrocarbon receptor ligand ITE inhibits TGFβ1-induced human myofibroblast differentiation.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Cell-Specific Modulation of the Aryl Hydrocarbon Receptor by Kynurenine in Pulmonary Fibrosis Requires Microenvironmental Crosstalk.bioRxiv : the preprint server for biology · 2026Article
- The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions.Clinical reviews in allergy & immunology · 2026Review
- Gut microbiota-derived metabolites and host interactions in fibrotic diseases: mechanisms, cross-organ signatures, and therapeutic opportunities.Frontiers in microbiology · 2026Review
- Asthma and inflammation transcriptionally up-regulate the aryl hydrocarbon receptor in airway smooth muscle via p38/JNK-AP1 signalling.British journal of pharmacology · 2025Article
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- Triggering AHR resolves TGF-β1 induced fibroblast activation and promotes AT1 cell regeneration in alveolar organoids.Communications biology · 2025Article
- CD103+ dendritic cell-fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis.JCI insight · 2025Article
- Transcriptomic profiling of thyroid eye disease orbital fat demonstrates differences in adipogenicity and IGF-1R pathway.JCI insight · 2024Article
- Aryl hydrocarbon receptor restricts axon regeneration of DRG neurons in response to injury.bioRxiv : the preprint server for biology · 2024Article
- Effects of atorvastatin on the function of Tenon's capsule fibroblasts in human eyes.International ophthalmology · 2023Article
- Disruption of the tumor suppressor-like activity of aryl hydrocarbon receptor by arsenic in epithelial cells and human lung cancer.International journal of biological sciences · 2023Article
- Dietary AhR Ligands Have No Anti-Fibrotic Properties in TGF-β1-Stimulated Human Colonic Fibroblasts.Nutrients · 2022Article
- Diet in Intestinal Fibrosis: A Double-Edged Sword.Nutrients · 2021Review
- Aryl hydrocarbon receptor signals attenuate lung fibrosis in the bleomycin-induced mouse model for pulmonary fibrosis through increase of regulatory T cells.Arthritis research & therapy · 2020Article
- The Smad2/3/4 complex binds miR-139 promoter to modulate TGFβ-induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway.Journal of cellular physiology · 2019Article
- Proton pump inhibitors attenuate myofibroblast formation associated with thyroid eye disease through the aryl hydrocarbon receptor.PloS one · 2019Article
- Tryptophan metabolites kynurenine and serotonin regulate fibroblast activation and fibrosis.Cellular and molecular life sciences : CMLS · 2018Review
- An endogenous aryl hydrocarbon receptor ligand, ITE, induces regulatory T cells and ameliorates experimental colitis.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Glyteer, Soybean Tar, Impairs IL-4/Stat6 Signaling in Murine Bone Marrow-Derived Dendritic Cells: The Basis of Its Therapeutic Effect on Atopic Dermatitis.International journal of molecular sciences · 2018Article
- ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR.Reproductive toxicology (Elmsford, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibrosis can occur in any human tissue when the normal wound healing response is amplified. Such amplification results in fibroblast proliferation, myofibroblast differentiation, and excessive extracellular matrix deposition. Occurrence of these sequelae in organs such as the eye or lung can result in severe consequences to health. Unfortunately, medical treatment of fibrosis is limited by a lack of safe and effective therapies. These therapies may be developed by identifying agents that inhibit critical steps in fibrotic progression; one such step is myofibroblast differentiation triggered by transforming growth factor-β1 (TGFβ1). In this study, we demonstrate that TGFβ1-induced myofibroblast differentiation is blocked in human fibroblasts by a candidate endogenous aryl hydrocarbon receptor (AhR) ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Our data show that ITE disrupts TGFβ1 signaling by inhibiting the nuclear translocation of Smad2/3/4. Although ITE functions as an AhR agonist, and biologically persistent AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, cause severe toxic effects, ITE exhibits no toxicity. Interestingly, ITE effectively inhibits TGFβ1-driven myofibroblast differentiation in AhR(-/-) fibroblasts: Its ability to inhibit TGFβ1 signaling is AhR independent. As supported by the results of this study, the small molecule ITE inhibits myofibroblast differentiation and may be useful clinically as an antiscarring agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.