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A mechanosensitive transcriptional mechanism that controls angiogenesis

Author

Listed:
  • Akiko Mammoto

    (Vascular Biology Program)

  • Kip M. Connor

    (Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Tadanori Mammoto

    (Vascular Biology Program)

  • Chong Wing Yung

    (Vascular Biology Program)

  • Dongeun Huh

    (Vascular Biology Program)

  • Christopher M. Aderman

    (Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Gustavo Mostoslavsky

    (Harvard Medical School, Harvard Institute of Medicine, Boston, Massachusetts 02215, USA
    Present address: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.)

  • Lois E. H. Smith

    (Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Donald E. Ingber

    (Vascular Biology Program
    Wyss Institute for Biologically Inspired Engineering and Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts 02138, USA)

Abstract

Angiogenesis is controlled by physical interactions between cells and extracellular matrix as well as soluble angiogenic factors, such as VEGF. However, the mechanism by which mechanical signals integrate with other microenvironmental cues to regulate neovascularization remains unknown. Here we show that the Rho inhibitor, p190RhoGAP (also known as GRLF1), controls capillary network formation in vitro in human microvascular endothelial cells and retinal angiogenesis in vivo by modulating the balance of activities between two antagonistic transcription factors, TFII-I (also known as GTF2I) and GATA2, that govern gene expression of the VEGF receptor VEGFR2 (also known as KDR). Moreover, this new angiogenesis signalling pathway is sensitive to extracellular matrix elasticity as well as soluble VEGF. This is, to our knowledge, the first known functional cross-antagonism between transcription factors that controls tissue morphogenesis, and that responds to both mechanical and chemical cues.

Suggested Citation

  • Akiko Mammoto & Kip M. Connor & Tadanori Mammoto & Chong Wing Yung & Dongeun Huh & Christopher M. Aderman & Gustavo Mostoslavsky & Lois E. H. Smith & Donald E. Ingber, 2009. "A mechanosensitive transcriptional mechanism that controls angiogenesis," Nature, Nature, vol. 457(7233), pages 1103-1108, February.
    • Handle: RePEc:nat:nature:v:457:y:2009:i:7233:d:10.1038_nature07765
    DOI: 10.1038/nature07765
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    Cited by:

    1. René F M van Oers & Elisabeth G Rens & Danielle J LaValley & Cynthia A Reinhart-King & Roeland M H Merks, 2014. "Mechanical Cell-Matrix Feedback Explains Pairwise and Collective Endothelial Cell Behavior In Vitro," PLOS Computational Biology, Public Library of Science, vol. 10(8), pages 1-14, August.
    2. Kevin D Webster & Ailey Crow & Daniel A Fletcher, 2011. "An AFM-Based Stiffness Clamp for Dynamic Control of Rigidity," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-7, March.

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