ArticleJCI insight2018
Fatty acid receptor modulator PBI-4050 inhibits kidney fibrosis and improves glycemic control.
Article in JCI insight, 2018. 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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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.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026Review
- Lipid metabolic dysregulation in diabetic kidney disease: mechanisms, cellular impact, and therapeutic strategies.Journal of clinical & translational endocrinology · 2026Review
- Discovery, Structure-Activity Relationship, and Functional Characterization of a Chromenopyrrole Series as Orthosteric Antagonists of GPR84.Journal of medicinal chemistry · 2026Article
- Medium-Chain Fatty Acid Receptor GPR84 Modulates Cytotoxic CD8 T-cell Antitumor Immunity through Metabolic Reprogramming.Cancer immunology research · 2026Article
- Renal Protection of HWL-088and ZLY-032, Two Dual GPR40/PPARδ Agonists, in Adenine-Induced Renal Fibrosis Model.Chemistry & biodiversity · 2025Article
- Molecular mechanism of renal lipid accumulation in diabetic kidney disease.Journal of cellular and molecular medicine · 2024Review
- Definition of fatty acid transport protein-2 (FATP2) structure facilitates identification of small molecule inhibitors for the treatment of diabetic complications.International journal of biological macromolecules · 2023Article
- Review
- Therapeutic validation of an orphan G protein-coupled receptor: The case of GPR84.British journal of pharmacology · 2022Review
- Myeloid cells in COVID-19 microenvironment.Signal transduction and targeted therapy · 2021Review
- Ventricular arrhythmias in mouse models of diabetic kidney disease.Scientific reports · 2021Article
- Pharmacology of Free Fatty Acid Receptors and Their Allosteric Modulators.International journal of molecular sciences · 2021Review
- Update on the Mechanisms of Tubular Cell Injury in Diabetic Kidney Disease.Frontiers in medicine · 2021Review
- Fatty acid transport protein-2 regulates glycemic control and diabetic kidney disease progression.JCI insight · 2020Article
- The New Biology of Diabetic Kidney Disease-Mechanisms and Therapeutic Implications.Endocrine reviews · 2020Review
- Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.Trends in pharmacological sciences · 2020Review
- Glycemic control is associated with atrial structural remodeling in patients with type 2 diabetes.BMC cardiovascular disorders · 2019Article
- Increased lipogenesis and impaired β-oxidation predict type 2 diabetic kidney disease progression in American Indians.JCI insight · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment). PBI-4050 treatment ameliorated the fasting hyperglycemia and abnormal glucose tolerance tests seen in vehicle-treated mice. In addition, PBI-4050 preserved (early treatment) or restored (late treatment) blood insulin levels and increased autophagy in islets. PBI-4050 treatment led to significant improvements in lifespan in the diabetic mice. Both early and late PBI-4050 treatment protected against progression of DN, as indicated by reduced histological glomerular injury and albuminuria, slow decline of glomerular filtration rate, and loss of podocytes. PBI-4050 inhibited kidney macrophage infiltration, oxidative stress, and TGF-β-mediated fibrotic signaling pathways, and it also protected against the development of tubulointerstitial fibrosis. To confirm a direct antiinflammatory/antifibrotic effect in the kidney, further studies with a nondiabetic model of EGFR-mediated proximal tubule activation confirmed that PBI-4050 dramatically decreased the development of the associated tubulointerstitial injury and macrophage infiltration. These studies suggest that PBI-4050 attenuates development of DN in type 2 diabetes through improvement of glycemic control and inhibition of renal TGF-β-mediated fibrotic pathways, in association with decreases in macrophage infiltration and oxidative stress.
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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.