PMID- 12680875 OWN - NLM STAT- MEDLINE DCOM- 20030513 LR - 20220316 IS - 0960-7722 (Print) IS - 1365-2184 (Electronic) IS - 0960-7722 (Linking) VI - 36 IP - 2 DP - 2003 Apr TI - 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. PG - 75-86 AB - 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. FAU - Neuhaus, Thomas AU - Neuhaus T AD - Medizinische Universitats-Poliklinik Bonn, Bonn, Germany. FAU - Stier, Sebastian AU - Stier S FAU - Totzke, Gudrun AU - Totzke G FAU - Gruenewald, Elisabeth AU - Gruenewald E FAU - Fronhoffs, Stefan AU - Fronhoffs S FAU - Sachinidis, Agapios AU - Sachinidis A FAU - Vetter, Hans AU - Vetter H FAU - Ko, Yon D AU - Ko YD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Prolif JT - Cell proliferation JID - 9105195 RN - 0 (CXCL12 protein, human) RN - 0 (Chemokine CXCL12) RN - 0 (Chemokines, CXC) RN - 0 (DNA-Binding Proteins) RN - 0 (EGR1 protein, human) RN - 0 (Early Growth Response Protein 1) RN - 0 (Endothelial Growth Factors) RN - 0 (Enzyme Inhibitors) RN - 0 (Immediate-Early Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Lymphokines) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Vascular Endothelial Growth Factors) RN - 9007-49-2 (DNA) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Arteries/cytology MH - Cell Division/drug effects MH - Cells, Cultured MH - Chemokine CXCL12 MH - Chemokines, CXC/*pharmacology MH - DNA/biosynthesis MH - DNA-Binding Proteins/*biosynthesis/genetics MH - Drug Synergism MH - Early Growth Response Protein 1 MH - Endothelial Growth Factors/*biosynthesis/*pharmacology/physiology MH - Endothelium, Vascular/drug effects/enzymology/*metabolism MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation MH - Humans MH - *Immediate-Early Proteins MH - Intercellular Signaling Peptides and Proteins/*biosynthesis/*pharmacology/physiology MH - Kinetics MH - Lymphokines/*biosynthesis/*pharmacology/physiology MH - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/metabolism MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - Phosphorylation MH - RNA, Messenger/biosynthesis MH - Transcription Factors/*biosynthesis/genetics MH - Vascular Endothelial Growth Factor A MH - Vascular Endothelial Growth Factors MH - p38 Mitogen-Activated Protein Kinases PMC - PMC6496392 EDAT- 2003/04/12 05:00 MHDA- 2003/05/14 05:00 PMCR- 2003/04/04 CRDT- 2003/04/12 05:00 PHST- 2003/04/12 05:00 [pubmed] PHST- 2003/05/14 05:00 [medline] PHST- 2003/04/12 05:00 [entrez] PHST- 2003/04/04 00:00 [pmc-release] AID - 262 [pii] AID - CPR262 [pii] AID - 10.1046/j.1365-2184.2003.00262.x [doi] PST - ppublish SO - Cell Prolif. 2003 Apr;36(2):75-86. doi: 10.1046/j.1365-2184.2003.00262.x.