ArticleDiabetes2010
Ablation of 4E-BP1/2 prevents hyperglycemia-mediated induction of VEGF expression in the rodent retina and in Muller cells in culture.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Stage-dependent signaling networks and therapeutic strategies in diabetic retinopathy: from neurovascular dysfunction to angiogenesis and fibrosis.Molecular biology reports · 2026Review
- Maternal Risk Factors for Retinopathy of Prematurity in Korea: A Nationwide Population-Based Study.Ophthalmology science · 2026Article
- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Article
- Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy.Translational vision science & technology · 2025Article
- The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024Review
- Post-transcriptional control by RNA-binding proteins in diabetes and its related complications.Frontiers in physiology · 2022Review
- Sequential and Dynamic Variations of IL-6, CD18, ICAM, TNF-Disease markers · 2022Article
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- 5'-UTR recruitment of the translation initiation factor eIF4GI or DAP5 drives cap-independent translation of a subset of human mRNAs.The Journal of biological chemistry · 2020Article
- Diabetes enhances translation ofThe Journal of biological chemistry · 2020Article
- Article
- One month of hyperglycemia alters spectral responses of the zebrafish photopic electroretinogram.Disease models & mechanisms · 2018Article
- Emerging roles of RNA-binding proteins in diabetes and their therapeutic potential in diabetic complications.Wiley interdisciplinary reviews. RNA · 2018Review
- Effect of intravitreal injection of ranibizumab on retinal ganglion cells and microvessels in the early stage of diabetic retinopathy in rats with streptozotocin-induced diabetes.Experimental and therapeutic medicine · 2017Article
- Retinal oxygen: from animals to humans.Progress in retinal and eye research · 2017Review
- Development of diabetes-induced acidosis in the rat retina.Experimental eye research · 2016Article
- Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells.Cellular signalling · 2016Article
- The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction.Investigative ophthalmology & visual science · 2016Article
- Angiogenesis in diabetes and obesity.Reviews in endocrine & metabolic disorders · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveVascular endothelial growth factor (VEGF) contributes to diabetic retinopathy, but control of its expression is not well understood. Here, we tested the hypothesis that hyperglycemia mediates induction of VEGF expression in a eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP) 1 and 2 dependent manner. RESEARCH DESIGN AND
methodsThe retina was harvested from control and type 1 diabetic rats and mice and analyzed for VEGF mRNA and protein expression as well as biomarkers of translational control mechanisms. Similar analyses were performed in Müller cell cultures exposed to hyperglycemic conditions. The effect of 4E-BP1 and 4E-BP2 gene deletion on VEGF expression was examined in mice and in mouse embryo fibroblasts (MEFs).
resultsWhereas VEGF mRNA in the retina remained constant, VEGF expression was increased as early as 2 weeks after the onset of diabetes. Increases in expression of 4E-BP1 protein mirrored those of VEGF and expression of 4E-BP1 mRNA was unchanged. Similar results were observed after 10 h of exposure of cells in culture to hyperglycemic conditions. Importantly, the diabetes-induced increase in VEGF expression was not observed in mice deficient in 4E-BP1 and 4E-BP2, nor in MEFs lacking the two proteins.
conclusionsHyperglycemia induces VEGF expression through cap-independent mRNA translation mediated by increased expression of 4E-BP1. Because the VEGF mRNA contains two internal ribosome entry sites, the increased expression is likely a consequence of ribosome loading at these sites. These findings provide new insights into potential targets for treatment of diabetic retinopathy.
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