Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway.
Stromal cell-derived factor (SDF)-1alpha, a member of the chemokine CXC subfamily, plays an important role in regulation of a variety of cellular functions of endothelial progenitor cells such as cell migration, proliferation, survival and angiogenesis. However, there is relatively little information linking the cellular functions and individual signaling pathways mediated by SDF-1alpha in endothelial progenitor cells. In our study, we showed that endothelial progenitor cells expressed CXCR4 by reverse transcription polymerase chain reaction and flow cytometric analysis. Functional analysis showed that SDF-1alpha induced a concentration-dependent migration of endothelial progenitor cells and the migration was CXCR4 dependent as confirmed by the total inhibition by AMD3100, a CXCR4-specific peptide antagonist. The migration can also be nearly completely blocked by phosphoinositide 3-kinase inhibitors (LY294002 and wortmannin) and eNOS inhibitor (N-nitro-arginine methyl ester), whereas mitogen-activated protein kinase/ERK inhibitor (PD98059) had no significant effect on SDF-1alpha-induced migration. The treatment of endothelial progenitor cells with SDF-1alpha resulted in time and concentration-dependent Akt, eNOS, and ERK1/2 phosphorylation. These findings suggested that phosphoinositide 3-kinase/Akt/eNOS, but not mitogen-activated protein kinase/ERK, signal transduction pathway may be involved in SDF-1alpha mediated migration of endothelial progenitor cells.
Zheng
Hao
H
Department of Cardiovascular Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
Fu
Guosheng
G
Dai
Tao
T
Huang
He
H
D001596:Benzylamines; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D000080027:Cyclams; D004730:Endothelium, Vascular / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors
D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D048049:Extracellular Signal-Regulated MAP Kinases; D006571:Heterocyclic Compounds; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019718:Receptors, CXCR4; C088327:plerixafor