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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3760-3765. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-04-1272. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2003-04-1272v1 103/10/3760    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oike, Y. Articles by Suda, T. Search for Related Content PubMed PubMed Citation Articles by Oike, Y. Articles by Suda, T. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Angiopoietin-related growth factor (AGF) promotes angiogenesis Yuichi Oike, Yasuhiro Ito, Hiromitsu Maekawa, Tohru Morisada, Yoshiaki Kubota, Masaki Akao, Takashi Urano, Kunio Yasunaga, and 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. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: AGF will make you blush Francesco Bertolini Blood 2004 103: 3610-3611. [Full Text] [PDF] This article has been cited by other articles: T. Urano, Y. Ito, M. Akao, T. Sawa, K. Miyata, M. Tabata, T. Morisada, T. Hato, M. Yano, T. Kadomatsu, et al. Angiopoietin-Related Growth Factor Enhances Blood Flow Via Activation of the ERK1/2-eNOS-NO Pathway in a Mouse Hind-Limb Ischemia Model Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 827 - 834. [Abstract] [Full Text] [PDF] M. Kitazawa, Y. Ohizumi, Y. Oike, T. Hishinuma, and S. Hashimoto Angiopoietin-Related Growth Factor Suppresses Gluconeogenesis through the Akt/Forkhead Box Class O1-Dependent Pathway in Hepatocytes J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 787 - 793. [Abstract] [Full Text] [PDF] S. Sasaki, T. Inoguchi, K. Muta, Y. Abe, M. Zhang, K. Hiasa, K. Egashira, N. Sonoda, K. Kobayashi, R. Takayanagi, et al. Therapeutic angiogenesis by ex vivo expanded erythroid progenitor cells Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H657 - H665. [Abstract] [Full Text] [PDF] K. Kobayashi, T. Kondo, N. Inoue, M. Aoki, M. Mizuno, K. Komori, J. Yoshida, and T. Murohara Combination of In Vivo Angiopoietin-1 Gene Transfer and Autologous Bone Marrow Cell Implantation for Functional Therapeutic Angiogenesis Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1465 - 1472. [Abstract] [Full Text] [PDF] Y. Kubota, Y. Oike, S. Satoh, Y. Tabata, Y. Niikura, T. Morisada, M. Akao, T. Urano, Y. Ito, T. Miyamoto, et al. Cooperative interaction of Angiopoietin-like proteins 1 and 2 in zebrafish vascular development PNAS, September 20, 2005; 102(38): 13502 - 13507. [Abstract] [Full Text] [PDF]

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