A mechanosensitive transcriptional mechanism that controls angiogenesis

作者：Mammoto Akiko; Connor Kip M; Mammoto Tadanori; Yung Chong Wing; Huh Dongeun; Aderman Christopher M; Mostoslavsky Gustavo; Smith Lois E H; Ingber Donald E^*

来源：Nature, 2009, 457(7233): 1103-U57.

DOI：10.1038/nature07765

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.

• 出版日期2009-2-26
• 单位河北医科大学