Stromal cell‐derived factor 1α (SDF‐1α) induces gene‐expression of early growth response‐1 (Egr‐1) and VEGF in human arterial endothelial cells and enhances VEGF induced cell proliferation

摘要

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‐1α 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‐1α. 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‐1α alone or together with VEGF. This particular test showed, that SDF‐1α alone has no effect, but is able to significantly enhance VEGF induced DNA synthesis. In summary, SDF‐1α 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.