Abstract
Vascular endothelial growth factor (VEGF-A) is a crucial stimulator of vascular cell migration and proliferation. Using bone marrow-derived human adult mesenchymal stem cells (MSCs) that did not express VEGF receptors, we provide evidence that VEGF-A can stimulate platelet-derived growth factor receptors (PDGFRs), thereby regulating MSC migration and proliferation. VEGF-A binds to both PDGFRalpha and PDGFRbeta and induces tyrosine phosphorylation that, when inhibited, results in attenuation of VEGF-A-induced MSC migration and proliferation. This mechanism was also shown to mediate human dermal fibroblast (HDF) migration. VEGF-A/PDGFR signaling has the potential to regulate vascular cell recruitment and proliferation during tissue regeneration and disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Bone Marrow Cells / cytology
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Bone Marrow Cells / metabolism*
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Cell Movement / drug effects
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Cell Movement / physiology
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Cells, Cultured
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Dermis / cytology
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Dermis / metabolism
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Female
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Humans
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Infant, Newborn
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Male
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / metabolism*
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Protein Binding / physiology
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Receptor, Platelet-Derived Growth Factor alpha / metabolism*
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Receptor, Platelet-Derived Growth Factor beta / metabolism*
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Regeneration / drug effects
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Regeneration / physiology
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Vascular Endothelial Growth Factor A / metabolism*
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Vascular Endothelial Growth Factor A / pharmacology
Substances
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Receptor, Platelet-Derived Growth Factor alpha
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Receptor, Platelet-Derived Growth Factor beta