ArticleCardiovascular research2012
VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution.
Article in Cardiovascular research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
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- Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Article
- Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
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- Aerobic exercise-induced circulating extracellular vesicle combined decellularized dermal matrix hydrogel facilitates diabetic wound healing by promoting angiogenesis.Frontiers in bioengineering and biotechnology · 2022Article
- The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis.International journal of molecular sciences · 2021Review
- LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis.Biomedicines · 2021Article
- Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications.International journal of molecular sciences · 2021Review
- Co-culture of ASCs/EPCs and dermal extracellular matrix hydrogel enhances the repair of full-thickness skin wound by promoting angiogenesis.Stem cell research & therapy · 2021Article
- uPAR: An Essential Factor for Tumor Development.Journal of Cancer · 2021Review
- The role of the oncostatin M/OSM receptor β axis in activating dermal microvascular endothelial cells in systemic sclerosis.Arthritis research & therapy · 2020Article
- Comparison of Proangiogenic Effects of Adipose-Derived Stem Cells and Foreskin Fibroblast Exosomes on Artificial Dermis Prefabricated Flaps.Stem cells international · 2020Article
- Controlled Delivery of Stem Cell-Derived Trophic Factors Accelerates Kidney Repair After Renal Ischemia-Reperfusion Injury in Rats.Stem cells translational medicine · 2019Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
aimsVascular endothelial growth factor (VEGF)-initiated angiogenesis requires coordinated proteolytic degradation of extracellular matrix provided by the urokinase plasminogen activator/urokinase receptor (uPA/uPAR) system and regulation of cell migration provided by integrin-matrix interaction. In this study, we investigated the mechanisms underlying the uPAR-dependent modulation of VEGF-induced endothelial migration. METHODS AND
resultsWe used flow cytometry to quantify integrins at the cell surface. Stimulation of human and murine endothelial cells with VEGF resulted in internalization of α5β1-integrins. Micropatterning and immunocytochemistry revealed co-clustering of uPAR and α5β1-integrins and retrieval via clathrin-coated vesicles. It was also contingent on receptors of the low-density lipoprotein receptor (LDL-R) family. VEGF-induced integrin redistribution was inhibited by elimination of uPAR from the endothelial cell surface or by inhibitory peptides that block the uPAR-integrin interaction. Under these conditions, the migratory response of endothelial cells upon VEGF stimulation was impaired both in vitro and in vivo.
conclusionsThe observations indicate that uPAR is an essential component of the network through which VEGF controls endothelial cell migration. uPAR is a bottleneck through which the VEGF-induced signal must be funnelled for both focused proteolytic activity at the leading edge and for redistribution of integrins.
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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.