title: Over-expression of PDGFR-β promotes PDGF-induced proliferation, migration, and angiogenesis of EPCs through PI3K/Akt signaling pathway.
abstract: 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.
authors.affiliation: Institute of Cardiovascular Science Xinqiao Hospital, Third Military Medical University, Shapingba District, Chongqing, People's Republic of China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Yangguang
authors.initials: Y
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Jinkun
authors.initials: J
authors.lastname: Zhu
authors.forename: Zhexue
authors.initials: Z
authors.lastname: Qin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D000077214:Becaplermin; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D018919:Neovascularization, Physiologic; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; D019870:1-Phosphatidylinositol 4-Kinase; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt