Abstract
Stromal cell-derived factor-1 (SDF-1), mainly known as a chemotactic factor for haematopoietic progenitor cells, also provides angiogenetic potency. Since the intracellular signalling of SDF-1-induced neovascularization remains unclear, we studied in human umbilical arterial endothelial cells (HUAEC) the influence of SDF-1alpha on induction of the genes of early growth response-1 (Egr-1) and VEGF, as well as the activation of extracellular regulated kinases (ERK) 1/2, which are all known to be involved in endothelial cell proliferation. We found a time-dependent induction of Egr-1 and VEGF mRNA expression and phosphorylation of ERK1/2 by SDF-1alpha. Furthermore, we demonstrated that Egr-1 expression is dependent on ERK 1/2 activation. Finally, we tried to confirm the relevance of the induced gene expression by detecting the [3H]thymidine incorporation as a marker for cell proliferation in HUAEC after stimulation with SDF-1alpha alone or together with VEGF. This particular test showed, that SDF-1alpha alone has no effect, but is able to significantly enhance VEGF induced DNA synthesis. In summary, SDF-1alpha is involved in different steps of endothelial cell proliferation, but, since Egr-1 and VEGF offer different functions, it may also play a so far undefined role on other conditions of the endothelium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arteries / cytology
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Cell Division / drug effects
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Cells, Cultured
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Chemokine CXCL12
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Chemokines, CXC / pharmacology*
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DNA / biosynthesis
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / genetics
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Drug Synergism
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Early Growth Response Protein 1
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Endothelial Growth Factors / biosynthesis*
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Endothelial Growth Factors / pharmacology*
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Endothelial Growth Factors / physiology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / metabolism*
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation
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Humans
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Immediate-Early Proteins*
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Intercellular Signaling Peptides and Proteins / biosynthesis*
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Intercellular Signaling Peptides and Proteins / pharmacology*
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Intercellular Signaling Peptides and Proteins / physiology
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Kinetics
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Lymphokines / biosynthesis*
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Lymphokines / pharmacology*
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Lymphokines / physiology
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylation
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RNA, Messenger / biosynthesis
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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p38 Mitogen-Activated Protein Kinases
Substances
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CXCL12 protein, human
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Chemokine CXCL12
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Chemokines, CXC
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DNA-Binding Proteins
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EGR1 protein, human
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Early Growth Response Protein 1
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Endothelial Growth Factors
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Enzyme Inhibitors
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Immediate-Early Proteins
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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RNA, Messenger
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Transcription Factors
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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DNA
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases