ArticleScientific reports2020
PPARα activation directly upregulates thrombomodulin in the diabetic retina.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Fibrates : Do They Still Have a Role in Therapy in 2025?Current atherosclerosis reports · 2025Review
- Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular Disease: Is There Still Room?Current atherosclerosis reports · 2025Review
- Expression and Secretion of Intraocular Fatty Acid-Binding Protein 4 (ioFABP4) and 5 (ioFABP5) Are Regulated by Glucose Levels and Fatty Acids.International journal of molecular sciences · 2025Article
- Future Directions in Diabetic Retinopathy Treatment: Stem Cell Therapy, Nanotechnology, and PPARα Modulation.Journal of clinical medicine · 2025Review
- Retinal ischemic diseases and promising therapeutic molecular targets.Histology and histopathology · 2025Review
- Pemafibrate Induces a Low Level of PPARα Agonist-Stimulated mRNA Expression of ANGPTL4 in ARPE19 Cell.Bioengineering (Basel, Switzerland) · 2024Article
- Lessons from PROMINENT and prospects for pemafibrate.Cardiovascular diabetology · 2024Article
- Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.Nutrients · 2023Review
- Pemafibrate, a potent selective peroxisome proliferator-activated receptor α modulator, a promising novel treatment for ischemic retinopathy?Neural regeneration research · 2023Article
- Therapeutic roles of PPARα activation in ocular ischemic diseases.Histology and histopathology · 2023Review
- Article
- Blood protein profiles related to preterm birth and retinopathy of prematurity.Pediatric research · 2022Article
- RNA-Binding Proteins and Alternative Splicing Genes Are Coregulated in Human Retinal Endothelial Cells Treated with High Glucose.Journal of diabetes research · 2022Article
- PPARα Modulation-Based Therapy in Central Nervous System Diseases.Life (Basel, Switzerland) · 2021Review
- Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy.Journal of clinical medicine · 2021Review
- Pemafibrate Prevents Retinal Dysfunction in a Mouse Model of Unilateral Common Carotid Artery Occlusion.International journal of molecular sciences · 2021Article
- Fenofibrate Protects against Retinal Dysfunction in a Murine Model of Common Carotid Artery Occlusion-Induced Ocular Ischemia.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Pemafibrate prevents retinal neuronal cell death in NMDA-induced excitotoxicity via inhibition of p-c-Jun expression.Molecular biology reports · 2021Article
- Small-Molecule Modulation of PPARs for the Treatment of Prevalent Vascular Retinal Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two large clinical studies showed that fenofibrate, a commonly used peroxisome proliferator-activated receptor α (PPARα) agonist, has protective effects against diabetic retinopathy. However, the underlying mechanism has not been clarified. We performed genome-wide analyses of gene expression and PPARα binding sites in vascular endothelial cells treated with the selective PPARα modulator pemafibrate and identified 221 target genes of PPARα including THBD, which encodes thrombomodulin (TM). ChIP-qPCR and luciferase reporter analyses showed that PPARα directly regulated THBD expression via binding to the promoter. In the rat diabetic retina, treatment with pemafibrate inhibited the expression of inflammatory molecules such as VCAM-1 and MCP1, and these effects were attenuated by intravitreal injection of small interfering RNA targeted to THBD. Furthermore, pemafibrate treatment inhibited diabetes-induced vascular leukostasis and leakage through the upregulation of THBD. Our results indicate that PPARα activation inhibits inflammatory and vasopermeable responses in the diabetic retina through the upregulation of TM.
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Registered trials
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