ArticleJournal of the American Society of Nephrology : JASN2017
Inhibition of Bromodomain and Extraterminal Domain Family Proteins Ameliorates Experimental Renal Damage.
Article in Journal of the American Society of Nephrology : JASN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Exosome-mediated renal protection: Halting the progression of fibrosis.Genes & diseases · 2024Review
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.Clinical and translational science · 2024Article
- BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study.Intensive care medicine experimental · 2024Article
- JQ1 attenuates contrast-induced acute kidney injury through the upregulation of autophagy and inhibition of inflammation.International urology and nephrology · 2024Article
- Inhibition of BRD4 Attenuates ER Stress-induced Renal Ischemic-Reperfusion Injury.International journal of biological sciences · 2024Article
- BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.Biomolecules · 2023Review
- BET Protein Inhibitor JQ1 Modulates Mitochondrial Dysfunction and Oxidative Stress Induced by Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2023Article
- The effect of JQ1 systemic administration on oxidative stress and apoptotic markers in renal ischemic reperfusion injury in a rat model.Journal of medicine and life · 2023Article
- Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis.International journal of molecular sciences · 2022Article
- Demethylation of H3K9 and H3K27 Contributes to the Tubular Renal Damage Triggered by Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Histone Acetylation and Modifiers in Renal Fibrosis.Frontiers in pharmacology · 2022Review
- A quinazoline-based bromodomain inhibitor, CN210, ameliorates indomethacin-induced ileitis in mice by inhibiting inflammatory cytokine expression.Drug development research · 2021Article
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats.Frontiers in pharmacology · 2021Article
- Pharmacological Modulation of BET Family in Sepsis.Frontiers in pharmacology · 2021Review
- BRDT is a novel regulator of eIF4EBP1 in renal cell carcinoma.Oncology reports · 2020Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal inflammation has a key role in the onset and progression of immune- and nonimmune-mediated renal diseases. Therefore, the search for novel anti-inflammatory pharmacologic targets is of great interest in renal pathology. JQ1, a small molecule inhibitor of bromodomain and extraterminal (BET) proteins, was previously found to preserve renal function in experimental polycystic kidney disease. We report here that JQ1-induced BET inhibition modulated the in vitro expression of genes involved in several biologic processes, including inflammation and immune responses. Gene silencing of BRD4, an important BET protein, and chromatin immunoprecipitation assays showed that JQ1 alters the direct association of BRD4 with acetylated histone-packaged promoters and reduces the transcription of proinflammatory genes (IL-6, CCL-2, and CCL-5). In vivo, JQ1 abrogated experimental renal inflammation in murine models of unilateral ureteral obstruction, antimembrane basal GN, and infusion of Angiotensin II. Notably, JQ1 downregulated the expression of several genes controlled by the NF-κB pathway, a key inflammatory signaling pathway. The RelA NF-κB subunit is activated by acetylation of lysine 310. In damaged kidneys and cytokine-stimulated renal cells, JQ1 reduced the nuclear levels of RelA NF-κB. Additionally, JQ1 dampened the activation of the Th17 immune response in experimental renal damage. Our results show that inhibition of BET proteins reduces renal inflammation by several mechanisms: chromatin remodeling in promoter regions of specific genes, blockade of NF-κB pathway activation, and modulation of the Th17 immune response. These results suggest that inhibitors of BET proteins could have important therapeutic applications in inflammatory renal diseases.
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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.