ArticleAmerican journal of respiratory cell and molecular biology2019
Efficacy of Novel Highly Specific Bromodomain-Containing Protein 4 Inhibitors in Innate Inflammation-Driven Airway Remodeling.
Article in American journal of respiratory cell and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- Mechanisms and therapeutic strategies of asthma: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4.Nature communications · 2026Article
- IRF1 mediates airway epithelial innate memory through priming BRD4- EP300 activity.Frontiers in immunology · 2026Article
- Computational discovery of BRD4 inhibitors for neuroblastoma therapy using pharmacophore screening and molecular simulations.Scientific reports · 2025Article
- An orally bioavailable BRD4 inhibitor disrupts expansion of a pathogenic epithelial-mesenchymal niche in bleomycin-induced fibrosis.Respiratory research · 2025Article
- Orally Bioavailable BRD4 BD1 Inhibitor ZL0516 Effectively Suppresses Colonic Inflammation in Animal Models of Inflammatory Bowel Disease.ACS pharmacology & translational science · 2025Article
- Interactions between epithelial mesenchymal plasticity, barrier dysfunction and innate immune pathways shape the genesis of allergic airway disease.Expert review of respiratory medicine · 2025Review
- 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
- NF-κB/RelA signaling in secretoglobin progenitors mediates plasticity and MMP-induced barrier disruption in house dust mite-induced allergic asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Article
- Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.Frontiers in immunology · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- BRD4 as a Therapeutic Target in Pulmonary Diseases.International journal of molecular sciences · 2023Review
- Article
- Bromodomain-containing Protein 4 Regulates Innate Inflammation in Airway Epithelial Cells via Modulation of Alternative Splicing.bioRxiv : the preprint server for biology · 2023Article
- Bromodomain-containing Protein 4 regulates innate inflammation via modulation of alternative splicing.Frontiers in immunology · 2023Article
- Semi-automated micro-computed tomography lung segmentation and analysis in mouse models.MethodsX · 2023Article
- Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19.Seminars in cancer biology · 2022Review
- Selective bromodomain and extra-terminal bromodomain inhibitor inactivates macrophages and hepatic stellate cells to inhibit liver inflammation and fibrosis.Bioengineered · 2022Article
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13 authors at 6 institutions in 4 countries.
Funding
Abstract
NF-κB/RelA triggers innate inflammation by binding to bromodomain-containing protein 4 (BRD4), an atypical histone acetyltransferase (HAT). Although RelA·BRD4 HAT mediates acute neutrophilic inflammation, its role in chronic and functional airway remodeling is not known. We observed that BRD4 is required for Toll-like receptor 3 (TLR3)-mediated mesenchymal transition, a cell-state change that is characteristic of remodeling. We therefore tested two novel highly selective BRD4 inhibitors, ZL0420 and ZL0454, for their effects on chronic airway remodeling produced by repetitive TLR3 agonist challenges, and compared their efficacy with that of two nonselective bromodomain and extraterminal (BET) protein inhibitors, JQ1 and RVX208. We observed that ZL0420 and ZL0454 more potently reduced polyinosinic:polycytidylic acid-induced weight loss and fibrosis as assessed by microcomputed tomography and second harmonic generation microscopy. These measures correlated with the collagen deposition observed in histopathology. Importantly, the ZL inhibitors were more effective than the nonselective BET inhibitors at equivalent doses. The ZL inhibitors had significant effects on lung physiology, reversing TLR3-associated airway hyperresponsiveness and increasing lung compliance in vivo. At the molecular level, ZL inhibitors reduced elaboration of the transforming growth factor-β-induced growth program, thereby preventing mucosal mesenchymal transition and disrupting BRD4 HAT activity and complex formation with RelA. We also observed that ZL0454 treatment blocked polyinosinic:polycytidylic acid-associated expansion of the α-SMA1
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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.