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

Hang Wang; Yangguang Yin; Wei Li; Xiaohui Zhao; Yang Yu; Jinkun Zhu; Zhexue Qin; Qiang Wang; Kui Wang; Wei Lu; Jie Liu; Lan Huang

doi:10.1371/journal.pone.0030503

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

PLoS One. 2012;7(2):e30503. doi: 10.1371/journal.pone.0030503. Epub 2012 Feb 15.

Authors

Hang Wang¹, Yangguang Yin, Wei Li, Xiaohui Zhao, Yang Yu, Jinkun Zhu, Zhexue Qin, Qiang Wang, Kui Wang, Wei Lu, Jie Liu, Lan Huang

Affiliation

¹ Institute of Cardiovascular Science Xinqiao Hospital, Third Military Medical University, Shapingba District, Chongqing, People's Republic of China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1-Phosphatidylinositol 4-Kinase / genetics
1-Phosphatidylinositol 4-Kinase / metabolism*
Becaplermin
Blotting, Western
Cell Movement / drug effects
Cell Movement / physiology*
Cell Proliferation* / drug effects
Cells, Cultured
Endothelium, Vascular / cytology
Endothelium, Vascular / metabolism*
Enzyme Inhibitors
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Humans
Neovascularization, Physiologic*
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism*
Proto-Oncogene Proteins c-sis / genetics
Proto-Oncogene Proteins c-sis / metabolism*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Receptor, Platelet-Derived Growth Factor beta / genetics
Receptor, Platelet-Derived Growth Factor beta / metabolism*
Signal Transduction / drug effects
Stem Cells / cytology
Stem Cells / metabolism*

Substances

Enzyme Inhibitors
Proto-Oncogene Proteins c-sis
RNA, Messenger
Becaplermin
1-Phosphatidylinositol 4-Kinase
Receptor, Platelet-Derived Growth Factor beta
Proto-Oncogene Proteins c-akt