Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis

Koji Taniguchi, Ken Ichiro Sasaki, Kousuke Watari, Hideo Yasukawa, Tsutomu Imaizumi, Toranoshin Ayada, Fuyuki Okamoto, Takuma Ishizaki, Reiko Kato, Ri Ichiro Kohno, Hiroshi Kimura, Yasufumi Sato, Mayumi Ono, Yoshikazu Yonemitsu, Akihiko Yoshimura

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Sprouty proteins (Sproutys) inhibit receptor tyrosine kinase signaling and control various aspects of branching morphogenesis. In this study, we examined the physiological function of Sproutys in angiogenesis, using gene targeting and short-hairpin RNA (shRNA) knockdown strategies. Sprouty2 and Sprouty4 double knockout (KO) (DKO) mice were embryonic-lethal around E12.5 due to cardiovascular defects. The number of peripheral blood vessels, but not that of lymphatic vessels, was increased in Sprouty4 KO mice compared with wild-type (WT) mice. Sprouty4 KO mice were more resistant to hind limb ischemia and soft tissue ischemia than WT mice were, because Sprouty4 deficiency causes accelerated neovascularization. Moreover, suppression of Sprouty2 and Sprouty4 expression in vivo by shRNA targeting accelerated angiogenesis and has a therapeutic effect in a mouse model of hind limb ischemia. These data suggest that Sproutys are physiologically important negative regulators of angiogenesis in vivo and novel therapeutic targets for treating peripheral ischemic diseases. Copyright:

Original languageEnglish
Article numbere5467
JournalPloS one
Volume4
Issue number5
DOIs
Publication statusPublished - 2009 May 8

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Taniguchi, K., Sasaki, K. I., Watari, K., Yasukawa, H., Imaizumi, T., Ayada, T., Okamoto, F., Ishizaki, T., Kato, R., Kohno, R. I., Kimura, H., Sato, Y., Ono, M., Yonemitsu, Y., & Yoshimura, A. (2009). Suppression of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis. PloS one, 4(5), [e5467]. https://doi.org/10.1371/journal.pone.0005467