ArticleThe Journal of biological chemistry2012
Down-regulation of NF-κB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition.
Article in The Journal of biological chemistry, 2012. 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 114 papers.
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Who cites it
114 citing papers in PubMed, 206 citations in OpenAlex.
- Bromodomain dimers: A case study of BRD4 and family-wide AlphaFold predictions.Structural dynamics (Melville, N.Y.) · 2026Article
- Distal enhancers regulate mammalian early embryonic lineage differentiation through long-range interactions.Nucleic acids research · 2026Article
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- Promotion of HIV clearance by sensitization of HIV reservoirs to cell death.Frontiers in immunology · 2025Article
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy.eLife · 2024Article
- Identification of Novel Bromodomain-Containing Protein 4 (BRD4) Binders through 3D Pharmacophore-Based Repositioning Screening Campaign.Molecules (Basel, Switzerland) · 2024Article
- An Update on Viral Infection-Associated Collapsing Glomerulopathy.Advances in kidney disease and health · 2024Review
- Class IIa HDAC4 and HDAC7 cooperatively regulate gene transcription in Th17 cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Apabetalone (RVX-208): A Potential Epigenetic Therapy for the Treatment of Cardiovascular, Renal, Neurological, Viral, and Cancer Disorders.ACS pharmacology & translational science · 2024Review
- Differential responses of pulmonary vascular cells from PAH patients and controls to TNFα and the effect of the BET inhibitor JQ1.Respiratory research · 2023Article
- Bromodomain Interactions with Acetylated Histone 4 Peptides in the BRD4 Tandem Domain: Effects on Domain Dynamics and Internal Flexibility.Biochemistry · 2022Article
- HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Discovery, X-ray Crystallography, and Anti-inflammatory Activity of Bromodomain-containing Protein 4 (BRD4) BD1 Inhibitors Targeting a Distinct New Binding Site.Journal of medicinal chemistry · 2022Article
- Calming the cytokine storm of COVID-19 through inhibition of JAK2/STAT3 signaling.Drug discovery today · 2022Review
- Combinatorial inhibition of BTK, PI3K-AKT and BRD4-MYC as a strategy for treatment of mantle cell lymphoma.Molecular biomedicine · 2022Article
- Similarities and Differences between COVID-19-Associated Nephropathy and HIV-Associated Nephropathy.Kidney diseases (Basel, Switzerland) · 2022Review
- Recent Approaches to Targeting Canonical NFJournal of the American Society of Nephrology : JASN · 2021Review
- Low expression of HIV genes in podocytes accelerates the progression of diabetic kidney disease in mice.Kidney international · 2021Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
NF-κB-mediated inflammation is the major pathology in chronic kidney diseases, including HIV-associated nephropathy (HIVAN) that ultimately progresses to end stage renal disease. HIV infection in the kidney induces NF-κB activation, leading to the production of proinflammatory chemokines, cytokines, and adhesion molecules. In this study, we explored selective inhibition of NF-κB transcriptional activity by small molecule blocking NF-κB binding to the transcriptional cofactor BRD4, which is required for the assembly of the productive transcriptional complex comprising positive transcription elongation factor b and RNA polymerase II. We showed that our BET (Bromodomain and Extra-Terminal domain)-specific bromodomain inhibitor MS417, designed to block BRD4 binding to the acetylated NF-κB, effectively attenuates NF-κB transcriptional activation of proinflammatory genes in kidney cells treated with TNFα or infected by HIV. MS417 ameliorates inflammation and kidney injury in HIV-1 transgenic mice, an animal model for HIVAN. Our study suggests that BET bromodomain inhibition, targeting at the proinflammatory activity of NF-κB, represents a new therapeutic approach for treating NF-κB-mediated inflammation and kidney injury in HIVAN.
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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.