Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo |
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Authors: | Wei-Gan Shen Qing-Yu Xue Jun Zhu Ben-Shun Hu Yu Zhang Yi-Ding Wu Qing Su |
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Institution: | (1) Medical College of Yangzhou University, 16 Huai Hai Road, Yangzhou, 225000, Jiangsu Province, PR China;(2) Yangzhou Educational College, Yangzhou, PR China |
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Abstract: | MAGE-D1 is a member of the MAGE family of proteins, and functions as an adaptor that mediates multiple signaling pathways.
The current study for the first time provides evidence for a role of MAGE-D1 in the negative regulation of angiogenic activity
in vitro and in vivo models. Our findings showed that MAGE-D1 over-expression significantly suppressed the angiogenic key
events such as endothelial cell migration and invasion, adhesion on collagen I substrate, and in vitro differentiation into
tube-like structures under both normoxic and hypoxic conditions. MAGE-D1 over-expression also inhibited in vivo angiogenesis
in Matrigel plugs that were implanted subcutaneously in mice. With further experiments, we revealed that MAGE-D1 over-expression
disrupted actin cytoskeleton organization and lamellipodia formation, and down-regulated HIF-1-dependent gene expression in
endothelial cells under hypoxic conditions. These findings demonstrate a new function of MAGE-D1 in the regulation of angiogenesis
and provide new insight into the ability of MAGE-D1 to suppress the growth and angiogenic response of endothelial cells by
interfering with HIF-1-dependent gene expression, and actin cytoskeleton reorganization, suggesting that MAGE-D1 might be
a novel inhibitor of angiogenesis in vitro and in vivo. |
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Keywords: | Actin Adhesion Angiogenesis Hypoxia MAGE-D1 Migration |
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