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Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo

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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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Acknowledgements

We thank Prof. M. Hiraoka for 5×HRE/pGL3/VEGF/E1b. This work was supported in part by grants from Natural Science Foundation of the Department of Education of Jiangsu Province and the project of the Subjects Group for Life Science of Yangzhou University (China).

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Authors and Affiliations

  1. Medical College of Yangzhou University, 16 Huai Hai Road, Yangzhou, 225000, Jiangsu Province, PR China

    Wei-Gan Shen, Jun Zhu, Ben-Shun Hu, Yu Zhang, Yi-Ding Wu & Qing Su

  2. Yangzhou Educational College, Yangzhou, PR China

    Qing-Yu Xue

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Correspondence to Wei-Gan Shen.

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Shen, WG., Xue, QY., Zhu, J. et al. Inhibition of adenovirus-mediated human MAGE-D1 on angiogenesis in vitro and in vivo. Mol Cell Biochem 300, 89–99 (2007). https://doi.org/10.1007/s11010-006-9373-6

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