ArticleScience signaling2014
A ligand-independent VEGFR2 signaling pathway limits angiogenic responses in diabetes.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 133 citations in OpenAlex.
- Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects.The Journal of physiology · 2017Trial
- Exploring the neuroprotective mechanism of Tongqiao Huashuan granules in vascular dementia based on PLCγ1/IP3R signaling pathway.Frontiers in aging neuroscience · 2026Article
- Polymorphisms inBiomedicines · 2025Review
- Diet-induced obesity promotes endothelial cell desensitization to VEGF-A and permanent islet vessel dysfunction in mice.The Journal of clinical investigation · 2025Article
- Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease.American journal of physiology. Renal physiology · 2025Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Endothelial FOXM1 and Dab2 promote diabetic wound healing.JCI insight · 2025Article
- Mechanisms of glutamate metabolic function and dysfunction in vascular dementia.Neuroprotection (Chichester, England) · 2024Review
- Sophoridine Counteracts Obesity via Src-Mediated Inhibition of VEGFR Expression and PI3K/AKT Phosphorylation.International journal of molecular sciences · 2024Article
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
- LncRNA SNHG8 regulates the migration and angiogenesis of pHUVECs induced by high glucose via the TRPM7/ERKScientific reports · 2023Article
- Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis.Immunity · 2023Article
- Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2-driven tumor angiogenesis.Cancer medicine · 2023Article
- 3D-Printed Functional Hydrogel by DNA-Induced Biomineralization for Accelerated Diabetic Wound Healing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Empagliflozin Reverses Hyperglycemia-Induced Monocyte and Endothelial Dysfunction Primarily through Glucose Transport-Independent but Redox-Dependent Mechanisms.Journal of clinical medicine · 2023Article
- Angiogenesis in Wound Repair: Too Much of a Good Thing?Cold Spring Harbor perspectives in biology · 2022Review
- Effect of Platelet-Derived Growth Factor C on Mitochondrial Oxidative Stress Induced by High d-Glucose in Human Aortic Endothelial Cells.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Syndecan-2 selectively regulates VEGF-induced vascular permeability.Nature cardiovascular research · 2022Article
- βNature communications · 2022Article
- A thermoreversible antibacterial zeolite-based nanoparticles loaded hydrogel promotes diabetic wound healing via detrimental factor neutralization and ROS scavenging.Journal of nanobiotechnology · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Although vascular complications are a hallmark of diabetes, the molecular mechanisms that underlie endothelial dysfunction are unclear. We showed that reactive oxygen species generated from hyperglycemia promoted ligand-independent phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This VEGFR2 signaling occurred within the Golgi compartment and resulted in progressively decreased availability of VEGFR2 at the cell surface. Consequently, the responses of endothelial cells to exogenous VEGF in a mouse model of diabetes were impaired because of a specific deficiency of VEGFR2 at the cell surface, despite a lack of change in transcript abundance. Hyperglycemia-induced phosphorylation of VEGFR2 did not require intrinsic receptor kinase activity and was instead mediated by Src family kinases. The reduced cell surface abundance of VEGFR2 in diabetic mice was reversed by treatment with the antioxidant N-acetyl-L-cysteine, suggesting a causative role for oxidative stress. These findings uncover a mode of ligand-independent VEGFR2 signaling that can progressively lead to continuously muted responses to exogenous VEGF and limit angiogenic events.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.