Stromal cell-derived factor 1alpha (SDF-1alpha) induces gene-expression of early growth response-1 (Egr-1) and VEGF in human arterial endothelial cells and enhances VEGF induced cell proliferation.
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.
Neuhaus
Thomas
T
Medizinische Universitäts-Poliklinik Bonn, Bonn, Germany.
Stier
Sebastian
S
Totzke
Gudrun
G
Gruenewald
Elisabeth
E
Fronhoffs
Stefan
S
Sachinidis
Agapios
A
Vetter
Hans
H
Ko
Yon D
YD
D001158:Arteries / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D051766:Early Growth Response Protein 1; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000494:pharmacology* / Q000502:physiology; D007700:Kinetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000494:pharmacology* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases