Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway

• Published in: PloS one 2012-02, Vol.7 (2), p.e30503-e30503
• Main Authors: Wang, Hang, Yin, Yangguang, Li, Wei, Zhao, Xiaohui, Yu, Yang, Zhu, Jinkun, Qin, Zhexue, Wang, Qiang, Wang, Kui, Lu, Wei, Liu, Jie, Huang, Lan
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 1-Phosphatidylinositol 4-Kinase - genetics; 1-Phosphatidylinositol 4-Kinase - metabolism; Adenoviruses; AKT protein; Angiogenesis; Bioavailability; Biology; Blotting, Western; Brain cancer; Breast cancer; Cell Movement - drug effects; Cell Movement - physiology; Cell proliferation; Cell Proliferation - drug effects; Cells (biology); Cells, Cultured; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Genes; Humans; Inhibitors; Kinases; Laboratory animals; Localization; Medicine; Neovascularization, Physiologic; Overexpression; Phosphorylation - drug effects; Platelet-derived growth factor; Platelet-derived growth factor BB; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-sis - genetics; Proto-Oncogene Proteins c-sis - metabolism; Real-Time Polymerase Chain Reaction; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism; RNA, Messenger - genetics; Science; Signal transduction; Signal Transduction - drug effects; Smooth muscle; Spleen; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Studies; Vascular endothelial growth factor; Vascularization
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0030503

The proliferation, migration, and angiogenesis of endothelial progenitor cells (EPCs) play critical roles in postnatal neovascularization and re-endothelialization following vascular injury. Here we evaluated whether the over-expression of platelet-derived growth factor receptor-β (PDGFR-β) can enhance the PDGF-BB-stimulated biological functions of EPCs through the PDGFR-β/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We first confirmed the expression of endogenous PDGFR-β and its plasma membrane localization in spleen-derived EPCs. We then demonstrated that the PDGFR-β over-expression in EPCs enhanced the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. Using AG1295 (a PDGFR kinase inhibitor), LY294002 (a PI3K inhibitor), and sc-221226 (an Akt inhibitor), we further showed that the PI3K/Akt signaling pathway participates in the PDGF-BB-induced proliferation, migration, and angiogenesis of EPCs. In addition, the PI3K/Akt signaling pathway is required for PDGFR-β over-expression to enhance these PDGF-BB-induced phenotypes.