ArticleInternational journal of molecular sciences2019
Hypoxia Induced Heparan Sulfate Primes the Extracellular Matrix for Endothelial Cell Recruitment by Facilitating VEGF-Fibronectin Interactions.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Evaluating the CRP Interactome: Insights into Possible Novel Roles in Cellular Signaling and Tumorigenicity.Current issues in molecular biology · 2025Review
- Porcine Single-Eye Retinal Pigment Epithelium Cell Culture for Barrier and Polarity Studies.Cells · 2025Article
- Ex Vivo Preconditioning as a Useful Tool for Modification of the Extracellular Matrix of Multipotent Mesenchymal Stromal Cells.International journal of molecular sciences · 2025Review
- Shaping Oncogenic Microenvironments: Contribution of Fibronectin.Frontiers in cell and developmental biology · 2024Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- ADAMTS18Nature communications · 2022Article
- Context Dependent Sulf1/Sulf2 Functional Divergence in Endothelial Cell Activity.International journal of molecular sciences · 2022Article
- The interactions between integrin αInternational journal of biological sciences · 2022Article
- All-trans retinoic acid regulating angiopoietins-1 and alleviating extracellular matrix accumulation in interstitial fibrosis rats.Renal failure · 2021Article
- Differential Gene Set Enrichment Analysis: a statistical approach to quantify the relative enrichment of two gene sets.Bioinformatics (Oxford, England) · 2021Article
- Lysophosphatidic Acid and IL-6 Trans-signaling Interact via YAP/TAZ and STAT3 Signaling Pathways in Human Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2020Article
- Retinal Distribution and Extracellular Activity of Granzyme B: A Serine Protease That Degrades Retinal Pigment Epithelial Tight Junctions and Extracellular Matrix Proteins.Frontiers in immunology · 2020Article
- Blood Targets of Adjuvant Drugs Against COVID19.Journal of blood medicine · 2020Article
- Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway.BioMed research international · 2020Article
- VEGF and VEGFR2 bind to similar pH-sensitive sites on fibronectin, exposed by heparin-mediated conformational changes.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor-A (VEGF) is critical for the development, growth, and survival of blood vessels. Retinal pigmented epithelial (RPE) cells are a major source of VEGF in the retina, with evidence that the extracellular matrix (ECM)-binding forms are particularly important. VEGF associates with fibronectin in the ECM to mediate distinct signals in endothelial cells that are required for full angiogenic activity. Hypoxia stimulates VEGF expression and angiogenesis; however, little is known about whether hypoxia also affects VEGF deposition within the ECM. Therefore, we investigated the role of hypoxia in modulating VEGF-ECM interactions using a primary retinal cell culture model. We found that retinal endothelial cell attachment to RPE cell layers was enhanced in cells maintained under hypoxic conditions. Furthermore, we found that agents that disrupt VEGF-fibronectin interactions inhibited endothelial cell attachment to RPE cells. We also found that hypoxia induced a general change in the chemical structure of the HS produced by the RPE cells, which correlated to changes in the deposition of VEGF in the ECM, and we further identified preferential binding of VEGFR2 over VEGFR1 to VEGF laden-fibronectin matrices. Collectively, these results indicate that hypoxia-induced HS may prime fibronectin for VEGF deposition and endothelial cell recruitment by promoting VEGF-VEGFR2 interactions as a potential means to control angiogenesis in the retina and other tissues.
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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.