ArticlePloS one2012
Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- PPARδ Agonist GW501516 Suppresses the TGF-β-Induced Profibrotic Response of Human Bronchial Fibroblasts from Asthmatic Patients.International journal of molecular sciences · 2023Article
- Mead acid inhibits retinol-induced irritant contact dermatitis via peroxisome proliferator-activated receptor alpha.Frontiers in molecular biosciences · 2023Article
- Keratinocyte-derived IL-1β induces PPARG downregulation and PPARD upregulation in human reconstructed epidermis following barrier impairment.Experimental dermatology · 2021Article
- PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming.International journal of molecular sciences · 2021Review
- Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy.Neuromolecular medicine · 2021Review
- Parsing the Role of PPARs in Macrophage Processes.Frontiers in immunology · 2021Review
- Discovery and Structure-Activity Relationships of Novel Template, Truncated 1'-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators.Journal of medicinal chemistry · 2020Article
- The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.Experimental eye research · 2020Article
- Peroxisomes and Oxidative Stress: Their Implications in the Modulation of Cellular Immunity During Mycobacterial Infection.Frontiers in microbiology · 2019Review
- Genomics of lipid-laden human hepatocyte cultures enables drug target screening for the treatment of non-alcoholic fatty liver disease.BMC medical genomics · 2018Article
- Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.Cell discovery · 2018Article
- Polypharmacology of NJournal of medicinal chemistry · 2017Article
- Nuclear receptor function in skin health and disease: therapeutic opportunities in the orphan and adopted receptor classes.Cellular and molecular life sciences : CMLS · 2016Review
- p53 activity contributes to defective interfollicular epidermal differentiation in hyperproliferative murine skin.The British journal of dermatology · 2016Article
- The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases.Cellular & molecular immunology · 2015Review
- The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state.Nucleic acids research · 2015Article
- RNA-seq identifies a role for the PPARβ/δ inverse agonist GSK0660 in the regulation of TNFα-induced cytokine signaling in retinal endothelial cells.Molecular vision · 2015Article
- Nuclear hormone receptor functions in keratinocyte and melanocyte homeostasis, epidermal carcinogenesis and melanomagenesis.FEBS letters · 2013Review
- Differential Expression of Endocannabinoid Receptors in Lesional and Non-Lesional Skin of Psoriasis Patients: Insights Into Pathogenesis and Potential Therapeutic Targets.Journal of cutaneous medicine and surgeryArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration.
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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.