ArticlePloS one2011
GW501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Progranulin impairs efferocytosis of macrophages in renal fibrosis by negatively regulating PPAR-δ-mediated inhibition of the JAK-STAT signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- The Role of Peroxisome Proliferator-Activated Receptors in Kidney Diseases.Frontiers in pharmacology · 2022Review
- Nuclear receptors in the kidney during health and disease.Molecular aspects of medicine · 2021Review
- The role of peroxisome proliferator-activated receptors (PPAR) in immune responses.Metabolism: clinical and experimental · 2021Review
- The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis.Experimental eye research · 2020Article
- Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- Pleiotropic Effects of PPARD Accelerate Colorectal Tumorigenesis, Progression, and Invasion.Cancer research · 2019Article
- Elafibranor Inhibits Chronic Kidney Disease Progression in NASH Mice.BioMed research international · 2019Article
- Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR Family Genes and Their Clinical Relevance in Patients with Major Trauma.International journal of environmental research and public health · 2016Article
- WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway.Laboratory investigation; a journal of technical methods and pathology · 2016Article
- Disruption of Lipid Raft Function Increases Expression and Secretion of Monocyte Chemoattractant Protein-1 in 3T3-L1 Adipocytes.PloS one · 2016Article
- 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
- The PPARβ/δ agonist GW501516 attenuates peritonitis in peritoneal fibrosis via inhibition of TAK1-NFκB pathway in rats.Inflammation · 2014Article
- Peroxisome proliferator-activated receptor-β/δ regulates angiogenic cell behaviors and oxygen-induced retinopathy.Investigative ophthalmology & visual science · 2013Article
- Article
- PPARδ agonist GW501516 inhibits PDGF-stimulated pulmonary arterial smooth muscle cell function related to pathological vascular remodeling.BioMed research international · 2013Article
- Article
- The renoprotective actions of peroxisome proliferator-activated receptors agonists in diabetes.PPAR research · 2012Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peroxisome proliferator-activated receptors (PPARs) are a nuclear receptor family of ligand-inducible transcription factors, which have three different isoforms: PPARα, δ and γ. It has been demonstrated that PPARα and γ agonists have renoprotective effects in proteinuric kidney diseases; however, the role of PPARδ agonists in kidney diseases remains unclear. Thus, we examined the renoprotective effect of GW501516, a PPARδ agonist, in a protein-overload mouse nephropathy model and identified its molecular mechanism. Mice fed with a control diet or GW501516-containing diet were intraperitoneally injected with free fatty acid (FFA)-bound albumin or PBS(-). In the control group, protein overload caused tubular damages, macrophage infiltration and increased mRNA expression of MCP-1 and TNFα. These effects were prevented by GW501516 treatment. In proteinuric kidney diseases, excess exposure of proximal tubular cells to albumin, FFA bound to albumin or cytokines such as TNFα is detrimental. In vitro studies using cultured proximal tubular cells showed that GW501516 attenuated both TNFα- and FFA (palmitate)-induced, but not albumin-induced, MCP-1 expression via direct inhibition of the TGF-β activated kinase 1 (TAK1)-NFκB pathway, a common downstream signaling pathway to TNFα receptor and toll-like receptor-4. In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases.
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