NDLI: Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3

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Vascular endothelial growth factor activation of endothelial cells is mediated by early growth response-3

Content Provider	Scilit
Author	Suehiro, Jun-Ichi Hamakubo, Takao Kodama, Tatsuhiko Aird, William C. Minami, Takashi
Copyright Year	2010
Description	Endothelial cell activation and dysfunction underlie many vascular disorders, including atherosclerosis, tumor growth, and sepsis. Endothelial cell activation, in turn, is mediated primarily at the level of gene transcription. Here, we show that in response to several activation agonists, including vascular endothelial growth factor (VEGF), tumor necrosis factor-α, and thrombin, endothelial cells demonstrate rapid and profound induction of the early growth response (Egr) genes egr-1 and egr-3. In VEGF-treated endothelial cells, induction of Egr-3 was far greater and more prolonged compared with Egr-1. VEGF-mediated stimulation of Egr-3 involved the inducible binding of NFATc, serum response factor, and CREB to their respective consensus motifs in the upstream promoter region of Egr-3. Knockdown of Egr-3 markedly impaired VEGF-mediated proliferation, migration, and tube formation of endothelial cells and blocked VEGF-induced monocyte adhesion. Egr-3 knockdown abrogated VEGF-mediated vascular outgrowth from ex vivo aortic rings and attenuated Matrigel plug vascularization and melanoma tumor growth in vivo. Together, these findings suggest that Egr-3 is a critical determinant of VEGF signaling in activated endothelial cells. Thus, Egr-3 represents a potential therapeutic target in VEGF-mediated vasculopathic diseases.
Related Links	http://www.bloodjournal.org/content/115/12/2520.full.pdf
Ending Page	2532
Page Count	13
Starting Page	2520
DOI	10.1182/blood-2009-07-233478
Journal	Blood
Issue Number	12
Volume Number	115
Language	English
Publisher	American Society of Hematology
Publisher Date	2010-03-25
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Endothelial Cells Tumor Growth Vascular Egr Endothelial Cell Activation Activation of Endothelial Vegf Mediated Journal: Blood (Vol- 121, Issue- 12)
Content Type	Text
Resource Type	Article

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