Regular Article
The Suppression of Small GTPase Rho Signal Transduction Pathway Inhibits Angiogenesis in Vitro and in Vivo

https://doi.org/10.1006/bbrc.2000.2315Get rights and content

Abstract

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

References (24)

  • C.D. Nobes et al.

    Cell

    (1995)
  • S. Narumiya et al.

    FEBS Lett.

    (1997)
  • S. Narumiya et al.

    J. Biol Chem.

    (1988)
  • A. Sekine et al.

    J. Biol. Chem.

    (1989)
  • D.H. Ausprunk et al.

    Dev. Biol.

    (1974)
  • T. Oikawa et al.

    Eur. J. Pharmacol.

    (1996)
  • D.S. Grant et al.

    Cell

    (1989)
  • H. Abedi et al.

    J. Biol. Chem.

    (1997)
  • N. Kumagai et al.

    J. Biol. Chem.

    (1993)
  • J.L. Gross et al.

    Proc. Natl. Acad. Sci. USA

    (1983)
  • B.R. Zetter

    Nature (London)

    (1980)
  • Cited by (0)

    View full text