ArticleInvestigative ophthalmology & visual science2014
O-GlcNAc modification of transcription factor Sp1 mediates hyperglycemia-induced VEGF-A upregulation in retinal cells.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.Nature genetics · 2016Pooled it
- Patient-specific iPSC-derived ECs identify QKI-7 as a key regulator of endothelial dysfunction and potential therapeutic target in diabetes.Stem cells translational medicine · 2026Article
- HMGA1 Lactylation-Mediated Regulation of the SP1/VEGFA Axis in Pathological Angiogenesis Under Diabetic Retinopathy.Diabetes · 2026Article
- Endothelial SP1 lactylation promotes bronchopulmonary dysplasia via regulation of Cdkn1a expression.Scientific reports · 2026Article
- Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription.Apoptosis : an international journal on programmed cell death · 2026Article
- Review
- Growth factor and hypoxia-inducible factor alpha content in the retina of male Wistar rats in experimental diabetic retinopathy and the effect of cellular protein kinase blockade.Frontiers in endocrinology · 2025Article
- The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovascular diabetology · 2023Review
- Posttranslational modifications of proteins in diseased retina.Frontiers in cellular neuroscience · 2023Review
- Connexins and Glucose Metabolism in Cancer.International journal of molecular sciences · 2022Review
- Review
- Analysis on the desert adaptability of indigenous sheep in the southern edge of Taklimakan Desert.Scientific reports · 2022Article
- Targeting ProteinCells · 2022Review
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- Laminar Flow on Endothelial Cells Suppresses eNOS O-GlcNAcylation to Promote eNOS Activity.Circulation research · 2021Article
- RUNX1 can mediate the glucose and O-GlcNAc-driven proliferation and migration of human retinal microvascular endothelial cells.BMJ open diabetes research & care · 2021Article
- Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders.The Biochemical journal · 2021Review
- Role of O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins in diabetic cardiovascular complications.Current opinion in pharmacology · 2021Review
- Diabetes enhances translation ofThe Journal of biological chemistry · 2020Article
- Increased expression of hypoxia inducible factor-1 alpha and vascular endothelial growth factor is associated with diabetic gastroparesis.BMC gastroenterology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeProangiogenic protein VEGF-A contributes significantly to retinal lesions and neovascularization in diabetic retinopathy (DR). In preclinical DR, hyperglycemia can upregulate VEGF-A in retinal cells. The VEGF-A promoter is responsive to the transcription factor specificity protein 1 (Sp1). The O-GlcNAc modification is driven by glucose concentration and has a profound effect on Sp1 activity. This study investigated the effects of hyperglycemia on Sp1-mediated expression of VEGF-A in the retinal endothelium and pigment epithelium.
methodsHyperglycemia-exposed ARPE-19 (human retinal pigment epithelial cells) and TR-iBRB (rat retinal microendothelial cells) were assayed for levels of VEGF-A by qRT-PCR, Western blot, and ELISA. Small molecule inhibitors of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA) were used to manipulate O-GlcNAc levels. Vascular endothelial growth factor-A protein and transcript were measured in cells depleted of OGT or Sp1 by shRNA. The proximal VEGF-A promoter was analyzed for glucose sensitivity by luciferase assay. Chromatin immunoprecipitation (ChIP) was used to assess Sp1 occupancy on the VEGF-A promoter.
resultsHyperglycemia increased VEGF-A promoter activity and upregulated VEGF-A transcript and protein. Elevation of O-GlcNAc by OGA inhibitors was sufficient to increase VEGF-A. O-GlcNAc transferase inhibition abrogated glucose-driven VEGF-A. Cellular depletion of OGT or Sp1 by shRNA significantly abrogated glucose-induced changes in VEGF-A. ChIP analysis showed that hyperglycemia significantly increased binding of Sp1 to the VEGF-A promoter.
conclusionsHyperglycemia-driven VEGF-A production is mediated by elevated O-GlcNAc modification of the Sp1 transcription factor. This mechanism may be significant in the pathogenesis of preclinical DR through VEGF-A upregulation.
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