ArticleThe Journal of biological chemistry2015
Regulated in development and DNA damage 1 is necessary for hyperglycemia-induced vascular endothelial growth factor expression in the retina of diabetic rodents.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Stage-dependent signaling networks and therapeutic strategies in diabetic retinopathy: from neurovascular dysfunction to angiogenesis and fibrosis.Molecular biology reports · 2026Review
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- Article
- Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2025Review
- Genetic Evidence Supporting a Causal Association Between mTORC1-Dependent Circulating Protein Levels and Diabetic Retinopathy.Translational vision science & technology · 2025Article
- Deletion of the stress response protein REDD1 prevents sodium iodate-induced RPE damage and photoreceptor loss.GeroScience · 2025Article
- A genome-wide scan of non-coding RNAs and enhancers for refractive error and myopia.Human genetics · 2025Article
- Review
- REDD1 Deletion Suppresses NF-κB Signaling in Cardiomyocytes and Prevents Deficits in Cardiac Function in Diabetic Mice.International journal of molecular sciences · 2024Article
- NLRP3 Inflammasome Priming in the Retina of Diabetic Mice Requires REDD1-Dependent Activation of GSK3β.Investigative ophthalmology & visual science · 2024Article
- The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.International journal of molecular sciences · 2024Review
- Shared signaling pathways and comprehensive therapeutic approaches among diabetes complications.Frontiers in medicine · 2024Review
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- The stress-responsive protein REDD1 and its pathophysiological functions.Experimental & molecular medicine · 2023Review
- PERK/ATF4-dependent expression of the stress response protein REDD1 promotes proinflammatory cytokine expression in the heart of obese mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Activation of Disulfide Redox Switch in REDD1 Promotes Oxidative Stress Under Hyperglycemic Conditions.Diabetes · 2022Article
- Blueberry Anthocyanins from Commercial Products: Structure Identification and Potential for Diabetic Retinopathy Amelioration.Molecules (Basel, Switzerland) · 2022Article
- Müller Glial Expression of REDD1 Is Required for Retinal Neurodegeneration and Visual Dysfunction in Diabetic Mice.Diabetes · 2022Article
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- Post-transcriptional control by RNA-binding proteins in diabetes and its related complications.Frontiers in physiology · 2022Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) is considered a major role player in the pathogenesis of diabetic retinopathy, yet the mechanisms regulating its expression are not fully understood. Our laboratory previously demonstrated that diabetes-induced VEGF expression in the retina was dependent on the repressor of mRNA translation 4E-BP1. Interaction of 4E-BP1 with the cap-binding protein eIF4E regulates protein expression by controlling the selection of mRNAs for translation. The process is regulated by the master kinase mTOR in complex 1 (mTORC1), which phosphorylates 4E-BP1, thus promoting its disassociation from eIF4E. In the present study, we investigated the role of the Akt/mTORC1 repressor REDD1 (regulated in development and DNA damage) in diabetes-induced VEGF expression. REDD1 expression was induced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in Müller cells concomitant with increased VEGF expression. In Müller cells, hyperglycemic conditions attenuated global rates of protein synthesis and cap-dependent mRNA translation concomitant with up-regulated cap-independent VEGF mRNA translation, as assessed by a bicistronic luciferase reporter assay. Hyperglycemic conditions also attenuated mTORC1 signaling and enhanced 4E-BP1 binding to eIF4E. Furthermore, ectopic expression of REDD1 in Müller cells was sufficient to promote both increased 4E-BP1 binding to eIF4E and VEGF expression. Whereas the retina of wild-type mice exhibited increased expression of VEGF and tumor necrosis factor alpha (TNF-α) 4 weeks after streptozotocin administration, the retina of REDD1 knock-out mice failed to do so. Overall, the results demonstrate that REDD1 contributes to the pathogenesis of diabetes in the retina by mediating the pathogenic effects of hyperglycemia.
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