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J. Cell Biol. 177 (3): 489-500

Copyright © 2007 by the Rockefeller University Press.

Article

Vascular endothelial growth factor can signal through platelet-derived growth factor receptors

Stephen G. Ball1,2, C. Adrian Shuttleworth2, , and Cay M. Kielty1,2

1 UK Centre for Tissue Engineering and 2 Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, England, UK

Correspondence to C. Adrian Shuttleworth: adrian.shuttleworth{at}manchester.ac.uk; or Cay M. Kielty: cay.kielty{at}manchester.ac.uk

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 PDGFR{alpha} and PDGFRß 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.

Abbreviations used in this paper: DTSSP, 3, 3'-Dithiobis[sulfosuccinimidyl propionate]; HDF, human dermal fibroblast; HUVEC, human umbilical vein endothelial cell; MSC, mesenchymal stem cell; NP, neuropilin; PDGFR, PDGF receptor; PVF, PDGF/VEGF-like factor; RTK, receptor tyrosine kinase; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

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