ArticlePloS one2011
Novel retinoic acid receptor alpha agonists for treatment of kidney disease.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 42 citations in OpenAlex.
- Identification of Spatial Specific Lipid Metabolic Signatures in Long-Standing Diabetic Kidney Disease.Metabolites · 2024Article
- Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhibition of retinoic acid signaling in proximal tubular epithelial cells protects against acute kidney injury.JCI insight · 2023Article
- Vitamin A and retinoid signaling in the kidneys.Pharmacology & therapeutics · 2023Review
- Anti-inflammatory Action of BT75, a Novel RARα Agonist, in Cultured Microglia and in an Experimental Mouse Model of Alzheimer's Disease.Neurochemical research · 2023Article
- New Boron Delivery Agents.Cancer biotherapy & radiopharmaceuticals · 2023Review
- Development of a New Methodology for Dearomative Borylation of Coumarins and Chromenes and Its Applications to Synthesize Boron-Containing Retinoids.Molecules (Basel, Switzerland) · 2023Article
- Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation.Frontiers in neuroscience · 2023Article
- Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.Molecules (Basel, Switzerland) · 2022Review
- Synthetic Retinoids Beyond Cancer Therapy.Annual review of pharmacology and toxicology · 2022Review
- Disparate roles of retinoid acid signaling molecules in kidney disease.American journal of physiology. Renal physiology · 2021Review
- Nuclear receptors in podocyte biology and glomerular disease.Nature reviews. Nephrology · 2021Review
- Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer's disease.Neural regeneration research · 2019Review
- Co-administration of retinoic acid and atorvastatin mitigates high-fat diet induced renal damage in rats.Veterinary research forum : an international quarterly journal · 2019Article
- Amelioration of Diabetic Nephropathy Using a Retinoic Acid ReceptorThe Journal of pharmacology and experimental therapeutics · 2018Article
- Increased podocyte Sirtuin-1 function attenuates diabetic kidney injury.Kidney international · 2018Article
- Retinoic acid improves nephrotoxic serum-induced glomerulonephritis through activation of podocyte retinoic acid receptor α.Kidney international · 2017Article
- Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis inAmerican journal of physiology. Renal physiology · 2017Article
- Radiolabeling and initial biological evaluation of [Bioorganic & medicinal chemistry letters · 2017Article
- Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.Nature biomedical engineering · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as 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.