ArticleCardiovascular diabetology2016
High glucose-induced hyperosmolarity contributes to COX-2 expression and angiogenesis: implications for diabetic retinopathy.
Article in Cardiovascular diabetology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- Fermented NaDES-Ginger Extract Attenuates Hyperglycemia-Driven Inflammation and Endothelial Adhesion in Colorectal Cancer Through the NF-κB/COX-2 Axis.Life (Basel, Switzerland) · 2026Article
- Engineered miR-122 inhibitors preserve endothelial mitochondrial function and prevent vascular dysfunction in obesity-associated prediabetes.Molecular therapy. Nucleic acids · 2026Article
- Neddylation-Mediated hnRNPA2B1 Degradation Aggravates Retinal Endothelial Cell Dysfunction in Diabetic Retinopathy by Regulating miR-93-5p/VEGFA.Investigative ophthalmology & visual science · 2026Article
- The NFAT5-AR Axis Is Associated with Hyperosmolarity, Renal Dysfunction, and Neutrophil-Related Inflammatory Markers in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- Neuroprotection in Diabetes Retinal Disease: An Unmet Medical Need.International journal of molecular sciences · 2026Review
- Diabetes-Driven Retinal Neurodegeneration: Its Role in the Pathogenesis of Diabetic Retinopathy.Biomedicines · 2025Review
- NFAT5 exacerbates β-cell ferroptosis by suppressing the transcription of PRDX2 in obese type 2 diabetes mellitus.Cellular and molecular life sciences : CMLS · 2025Article
- Inhibitory effects of ursolic acid on oxygen-induced mouse retinal neovascularization via intravitreal injection.Molecular vision · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Metabolic Shift and Hyperosmolarity Underlie Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Review
- Study on the bioactive ingredients and mechanism of Huangqi against diabetic retinopathy based on network pharmacology and experimental verification.Journal of the Chinese Medical Association : JCMA · 2024Article
- Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.International journal of molecular sciences · 2024Article
- Genetic insights and emerging therapeutics in diabetic retinopathy: from molecular pathways to personalized medicine.Frontiers in genetics · 2024Review
- Neuroprotective Effects of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors (Gliflozins) on Diabetes-Induced Neurodegeneration and Neurotoxicity: A Graphical Review.International journal of preventive medicine · 2024Review
- Endoplasmic reticulum stress: a novel targeted approach to repair bone defects by regulating osteogenesis and angiogenesis.Journal of translational medicine · 2023Review
- Inflammation in diabetic retinopathy: possible roles in pathogenesis and potential implications for therapy.Neural regeneration research · 2023Review
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration.Journal of functional biomaterials · 2023Article
- Response of a Human Lens Epithelial Cell Line to Hyperglycemic and Oxidative Stress: The Role of Aldose Reductase.Antioxidants (Basel, Switzerland) · 2023Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe tested the hypothesis that glucose-induced hyperosmolarity, occurring in diabetic hyperglycemia, promotes retinal angiogenesis, and that interference with osmolarity signaling ameliorates excessive angiogenesis and retinopathy in vitro and in vivo. METHODS AND
resultsWe incubated human aortic (HAECs) and dermal microvascular endothelial cells (HMVECs) with glucose or mannitol for 24 h and tested them for protein levels and in vitro angiogenesis. We used the Ins2 Akita mice as a model of type 1 diabetes to test the in vivo relevance of in vitro observations. Compared to incubations with normal (5 mmol/L) glucose concentrations, cells exposed to both high glucose and high mannitol (at 30.5 or 50.5 mmol/L) increased expression of the water channel aquaporin-1 (AQP1) and cyclooxygenase (COX)-2. This was preceded by increased activity of the osmolarity-sensitive transcription factor Tonicity enhancer binding protein (TonEBP), and enhanced endothelial migration and tubulization in Matrigel, reverted by treatment with AQP1 and TonEBP siRNA. Retinas of Ins2 Akita mice showed increased levels of AQP1 and COX-2, as well as angiogenesis, all reverted by AQP1 siRNA intravitreal injections.
conclusionsGlucose-related hyperosmolarity seems to be able to promote angiogenesis and retinopathy through activation of TonEBP and possibly increasing expression of AQP1 and COX-2. Osmolarity signaling may be a target for therapy.
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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.