ArticleTranslational research : the journal of laboratory and clinical medicine2017
Nrf2 exerts cell-autonomous antifibrotic effects: compromised function in systemic sclerosis and therapeutic rescue with a novel heterocyclic chalcone derivative.
Article in Translational research : the journal of laboratory and clinical medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Cellular and molecular dysregulation of the esophageal epithelium in systemic sclerosis.JCI insight · 2026Article
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- Emerging Therapeutic Strategies for Nrf2-Associated Skin Disorders: From Photoaging to Autoimmunity.Antioxidants (Basel, Switzerland) · 2026Review
- Mechanosensing regulates pDC activation in the skin through NRF2 activation.The Journal of experimental medicine · 2025Article
- Loss of Protein Kinase D2 Activity Protects Against Bleomycin-Induced Dermal Fibrosis in Mice.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Article
- Metabolic reprogramming of glycolysis and glutamine metabolism are key events in myofibroblast transition in systemic sclerosis pathogenesis.Journal of cellular and molecular medicine · 2020Article
- Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist.Scientific reports · 2020Article
- Understanding Fibrosis in Systemic Sclerosis: Novel and Emerging Treatment Approaches.Current rheumatology reports · 2020Review
- A Positive Feed Forward Loop between Wnt/Oxidative medicine and cellular longevity · 2020Article
- Complementary therapies for patients with systemic sclerosis.Journal of scleroderma and related disorders · 2019Review
- Emerging targets of disease-modifying therapy for systemic sclerosis.Nature reviews. Rheumatology · 2019Review
- The Protective Role of Tanshinone IIA in Silicosis Rat Model via TGF-β1/Smad Signaling Suppression, NOX4 Inhibition and Nrf2/ARE Signaling Activation.Drug design, development and therapy · 2019Article
- The Keap1/Nrf2-ARE Pathway as a Pharmacological Target for Chalcones.Molecules (Basel, Switzerland) · 2018Review
- Redox Imbalance in Intestinal Fibrosis: Beware of the TGFβ-1, ROS, and Nrf2 Connection.Digestive diseases and sciences · 2018Review
- NRF2 Activation Inhibits Both TGF-Oxidative medicine and cellular longevity · 2018Article
- Contribution of Nrf2 Modulation to the Mechanism of Action of Analgesic and Anti-inflammatory Drugs in Pre-clinical and Clinical Stages.Frontiers in pharmacology · 2018Review
- Inhibitory Effects of Momordicine I on High-Glucose-Induced Cell Proliferation and Collagen Synthesis in Rat Cardiac Fibroblasts.Oxidative medicine and cellular longevity · 2018Article
- Therapeutic Targeting of TAZ and YAP by Dimethyl Fumarate in Systemic Sclerosis Fibrosis.The Journal of investigative dermatology · 2018Article
- TheFrontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs antioxidant, innate immune and cytoprotective responses and its deregulation is prominent in chronic inflammatory conditions. To examine the hypothesis that Nrf2 might be implicated in systemic sclerosis (SSc), we investigated its expression, activity, and mechanism of action in SSc patient samples and mouse models of fibrosis and evaluated the effects of a novel pharmacologic Nrf2 agonist. We found that both expression and activity of Nrf2 were significantly reduced in SSc patient skin biopsies and showed negative correlation with inflammatory gene expression. In skin fibroblasts, Nrf2 mitigated fibrotic responses by blocking canonical transforming growth factor-β (TGF-β)-Smad signaling, whereas silencing Nrf2 resulted in constitutively elevated collagen synthesis, spontaneous myofibroblast differentiation, and enhanced TGF-ß responses. Bleomycin treatment of Nrf2-null mice resulted in exaggerated fibrosis. In wild-type mice, treatment with a novel pharmacologic Nrf2 agonist 2-trifluoromethyl-2'-methoxychalcone prevented dermal fibrosis induced by TGF-β. These findings are the first to identify Nrf2 as a cell-intrinsic antifibrotic factor with key roles in maintaining extracellular matrix homeostasis and a pathogenic role in SSc. Pharmacologic reactivation of Nrf2, therefore, represents a novel therapeutic strategy toward effective treatment of fibrosis in SSc.
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Registered trials
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