A mechanosensitive transcriptional mechanism that controls angiogenesis

Akiko Mammoto, Kip M. Connor, Tadanori Mammoto, Chong Wing Yung, Dongeun Huh, Christopher M. Aderman, Gustavo Mostoslavsky, Lois E. H. Smith and Donald E. Ingber ()
Additional contact information
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
Lois E. H. Smith: Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Donald E. Ingber: Vascular Biology Program

Nature, 2009, vol. 457, issue 7233, 1103-1108

Abstract: 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.

Date: 2009
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DOI: 10.1038/nature07765

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