HB-EGF promotes angiogenesis in endothelial cells via PI3-kinase and MAPK signaling pathways

Published on Aug 1, 2007in Growth Factors Journal1.543
· DOI :10.1080/08977190701773070
Veela B. Mehta15
Estimated H-index: 15
(The Research Institute at Nationwide Children's Hospital),
Gail E. Besner50
Estimated H-index: 50
(The Research Institute at Nationwide Children's Hospital)
Objective: Heparin-binding EGF-like growth factor (HB-EGF) belongs to the epidermal growth factor (EGF) superfamily of ligands. It has been implicated as a regulator of angiogenesis. However, the mechanisms by which HB-EGF promotes angiogenesis are unknown. The goal of the present study was to define the pathways by which HB-EGF stimulates angiogenesis in endothelial cells.Methods: To characterize the angiogenic activity of HB-EGF, we treated human umbilical vein endothelial cells (HUVEC) with HB-EGF and analyzed the effects on cell proliferation, migration and tube formation. Side-by-side assays with EGF were used for comparison.Results: Both HB-EGF and EGF stimulated HUVEC migration in scratch assays and promoted vascular tube formation in 2D-angiogenesis assays, without inducing cell proliferation. HB-EGF- and EGF-induced HUVEC migration and capillary tube formation were dependent upon activation of PI3K, MAPK and eNOS. Importantly, HB-EGF-and EGF-induced tube formation was comparable to, but were inde...
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