The Growth Factor Midkine Antagonizes VEGF Signaling In Vitro and In Vivo
Autor: | Edward Htun van der Horst, Brendon T. Frank, Lawrence Chinn, Angela Coxon, Shyun Li, Fanny Polesso, Anthony Slavin, Astrid Ruefli-Brasse, Holger Wesche |
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Jazyk: | angličtina |
Rok vydání: | 2008 |
Předmět: | |
Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 10, Iss 4, Pp 340-346 (2008) |
Druh dokumentu: | article |
ISSN: | 1476-5586 1522-8002 |
DOI: | 10.1593/neo.07820 |
Popis: | Midkine (MDK) is a heparin-binding growth factor involved in growth, survival, migration, and differentiation of various target cells and dysregulation of MDK signaling is implicated in a variety of inflammatory diseases and cancers. Although MDK has been reported to act on endothelial cells and to have proangiogenic effects, the exact role of MDK in angiogenesis is poorly defined. Here, we report that MDK is actually a modulator of angiogenesis and that it can abrogate the vascular endothelial growth factor A (VEGF-A)-induced proliferation of human microvascular endothelial cells in vitro through the downregulation of proangiogenic cytokines and through the upregulation of the antiangiogenic factor, tissue inhibitor of metalloproteinase 2. Phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2) and of downstream signaling molecules, such as phosphatidylinositol-3-kinase and mitogen-activated protein kinases, is also impaired. Moreover, MDK downregulates VEGF-A-induced neovascularization and vascular permeability in vivo. We propose a model in which MDK is a new modulator of the VEGF-A-VEGFR-2 axis. |
Databáze: | Directory of Open Access Journals |
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