ArticleJCI insight2020
Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- BRD4 Inhibition alleviates sepsis-associated acute kidney injury via suppression of NOX4-mediated oxidative stress and inflammation.Cell death discovery · 2026Article
- Review
- Bromodomain-containing protein 4 in inflammatory diseases: molecular mechanisms and therapeutic potential.Journal of inflammation (London, England) · 2026Review
- Inhalation-Based Nanoparticle Drug Delivery Targeting the Diseased Lower Airways in Idiopathic Pulmonary Fibrosis.Pharmaceutics · 2026Review
- Senescent fibroblasts in aging and pulmonary fibrosis.Frontiers in aging · 2026Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Decoding Bromodomain and Extra-Terminal Domain Protein-Mediated Epigenetic Mechanisms in Human Uterine Fibroids.International journal of molecular sciences · 2025Article
- Reprogramming oncogenic mitochondria in pancreatic adenocarcinoma through BRD4 inhibition leads to programmed cell death.The Journal of pharmacology and experimental therapeutics · 2025Article
- Histone H4 Lysine 12 Lactylation Promotes the Senescence of Alveolar Epithelial Type II Cells in Chronic Obstructive Pulmonary Disease by Modulating the CD38-NADAging and disease · 2025Article
- BRD4 Mediates Transforming Growth Factor-β-Induced Smooth Muscle Cell Differentiation from Mesenchymal Progenitor Cells.International journal of molecular sciences · 2025Article
- The Sound of Silence: Suppressing CBX5 Decreases Fibrosis by Inhibiting Fibroblasts.American journal of respiratory cell and molecular biology · 2025Article
- Epithelial Cell Dysfunction in Pulmonary Fibrosis: Mechanisms, Interactions, and Emerging Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription.Nature communications · 2025Article
- BRD4 Mediates Cadmium-Induced Oxidative Stress and Kidney Injury in Mice via Disruption of Redox Homeostasis.Toxics · 2025Article
- A Micro-Computed Tomography-Based Simplified Approach to Measure Body Composition, Osteoporosis, and Lung Fibrosis in Mice.Bio-protocol · 2025Article
- Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases.Journal of advanced research · 2024Review
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- Inhibition of CK2 Diminishes Fibrotic Scar Formation and Improves Outcomes After Ischemic Stroke via Reducing BRD4 Phosphorylation.Neurochemical research · 2024Article
- T-2 Toxin-Mediated β-Arrestin-1 O-GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Tissue regeneration capacity declines with aging in association with heightened oxidative stress. Expression of the oxidant-generating enzyme, NADPH oxidase 4 (Nox4), is elevated in aged mice with diminished capacity for fibrosis resolution. Bromodomain-containing protein 4 (Brd4) is a member of the bromodomain and extraterminal (BET) family of proteins that function as epigenetic "readers" of acetylated lysine groups on histones. In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. BET inhibition interferes with the association of Brd4, p300, and acetylated histone H4K16 with the Nox4 promoter in lung fibroblasts stimulated with the profibrotic cytokine, TGF-β1. A number of BET inhibitors, including I-BET-762, JQ1, and OTX015, downregulate Nox4 gene expression and activity. Aged mice with established and persistent lung fibrosis recover capacity for fibrosis resolution with OTX015 treatment. This study implicates epigenetic regulation of Nox4 by Brd4 and p300 and supports BET/Brd4 inhibition as an effective strategy for the treatment of age-related fibrotic lung disease.
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What OpenQuestion holds
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.