Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells

Journal of Cellular Physiology
C IwasakaY Sato

Abstract

The coordinate induction of protease activities and cell migration is a principal feature of endothelial cells (ECs) invading the interstitial space in the initial step of angiogenesis. However, the molecular mechanisms of these events are not fully characterized. Ets-1 is a member of the ets gene family of transcription factors, which binds to the Ets binding motif in the cis-acting elements and regulates the expression of certain genes. Four typical angiogenic growth factors, aFGF, bFGF, VEGF, and EGF, induced the expression of ets-1 mRNA in either human umbilical vein endothelial cells (HUVECs), ECV-304 cells (immortalized HUVECs), or human omental microvascular endothelial cells (HOMECs). The expression of ets-1 reached its maximum at 2 hr after factor addition and then decreased to the basal level by 12 hr. For characterization of the role of Ets-1 in angiogenesis, ets-1 antisense and sense oligodeoxynucleotides (ODNs) were constructed. The ets-1 antisense ODN but not sense ODN efficiently blocked the synthesis of Ets-1 protein by human ECs in response to angiogenic growth factors. Moreover, the ets-1 antisense ODN but not sense ODN almost completely abolished the binding of endothelial cell extract to DNA containing the E...Continue Reading

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