Ball Stephen G, Shuttleworth C Adrian, Kielty Cay M
UK Centre for Tissue Engineering and 2Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, The University of Manchester, Manchester, England, UK.
J Cell Biol. 2007 May 7;177(3):489-500. doi: 10.1083/jcb.200608093. Epub 2007 Apr 30.
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.
血管内皮生长因子(VEGF-A)是血管细胞迁移和增殖的关键刺激因子。利用不表达VEGF受体的骨髓来源的成人人类间充质干细胞(MSC),我们提供证据表明VEGF-A可刺激血小板衍生生长因子受体(PDGFR),从而调节MSC的迁移和增殖。VEGF-A与PDGFRα和PDGFRβ均结合并诱导酪氨酸磷酸化,当这种磷酸化受到抑制时,会导致VEGF-A诱导的MSC迁移和增殖减弱。该机制也被证明可介导人类皮肤成纤维细胞(HDF)的迁移。VEGF-A/PDGFR信号传导在组织再生和疾病过程中具有调节血管细胞募集和增殖的潜力。