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Publication : A mechanosensitive transcriptional mechanism that controls angiogenesis.

First Author  Mammoto A Year  2009
Journal  Nature Volume  457
Issue  7233 Pages  1103-8
PubMed ID  19242469 Mgi Jnum  J:145957
Mgi Id  MGI:3836365 Doi  10.1038/nature07765
Citation  Mammoto A, et al. (2009) A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457(7233):1103-8
abstractText  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.
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