Angiopoietin-related growth factor (AGF) promotes angiogenesis

• Yuichi Oike

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Yasuhiro Ito

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Hiromitsu Maekawa

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Tohru Morisada

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Yoshiaki Kubota

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Masaki Akao

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Takashi Urano

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Kunio Yasunaga

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

• Toshio Suda

  From the Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo, Japan; and Molecular Medicine Laboratories, Yamanouchi Pharmaceutical, Tsukuba, Japan.

抄録

We report here the identification of angiopoietin-related growth factor (AGF) as a positive mediator for angiogenesis. To investigate the biologic function of AGF in angiogenesis, we analyzed the vasculature in the dermis of transgenic mice expressing AGF in mouse epidermal keratinocytes (K14-AGF). K14-AGF transgenic mice were grossly red, especially in the ears and snout, suggesting that hypervascularization had occurred in their skin. Histologic examination of ear skin from K14-AGF transgenic mice revealed increased numbers of microvessels in the dermis, whereas the expression of several angiogenic factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factors (VEGFs), and angiopoietin-1 (Ang-1), was decreased. We showed that AGF is a secreted protein and does not bind to tyrosine kinase with immunoglobulin and EGF-homology domain (Tie1) or Tie2 receptors. An in vitro chamber assay revealed that AGF directly promotes chemotactic activity of vascular endothelial cells. Both mouse corneal and matrigel plug assays showed that AGF induces neovascularization in vivo. Furthermore, we found that plasma leakage occurred after direct injection of AGF into the mouse dermis, suggesting that AGF directly induces a permeability change in the local vasculature. On the basis of these observations, we propose that AGF is a novel angiogenic factor and that handling of its biologic functions could lead to novel therapeutic strategies for control of angiogenesis.

収録刊行物

• Blood

  Blood 103 (10), 3760-3765, 2004-05-15

  American Society of Hematology

キーワード

• Cell Biology
• Hematology
• Immunology
• Biochemistry

詳細情報

• CRID: 1363388843681390080
• NII論文ID: 30022497525
• DOI: 10.1182/blood-2003-04-1272
• ISSN: 15280020
• ISSN: 00064971
• Web Site: http://ashpublications.org/blood/article-pdf/103/10/3760/1697087/zh801004003760.pdf
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