A Mechanosensitive Transcriptional Mechanism That Controls Angiogenesis

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A Mechanosensitive Transcriptional Mechanism That Controls Angiogenesis

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dc.contributor.author Mammoto, Akiko
dc.contributor.author Connor, Kip
dc.contributor.author Mammoto, Tadanori
dc.contributor.author Yung, Chong W.
dc.contributor.author Huh, Dongeun
dc.contributor.author Aderman, Christopher Michael
dc.contributor.author Mostoslavsky, Gustavo
dc.contributor.author Smith, Lois Elaine Hodgson
dc.contributor.author Ingber, Donald Elliott
dc.date.accessioned 2010-02-02T17:38:24Z
dc.date.issued 2009
dc.identifier.citation Mammoto, Akiko, Kip M. Connor, Tadanori Mammoto, Chong Wing Yung, Dongeun Huh, Christopher Michael Aderman, Gustavo Mostoslavsky, Lois Elaine Hodgson Smith, and Donald Elliott Ingber. 2009. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457(7233): 1103-1108. en_US
dc.identifier.issn 0028-0836 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:3622234
dc.description.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. en_US
dc.description.sponsorship Engineering and Applied Sciences en_US
dc.language.iso en_US en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof doi:10.1038/nature07765 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3494&itool=Abstract-nondef&uid=19242469&nlmid=0410462&db=pubmed&url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19242469 en_US
dash.license META_ONLY
dc.subject TFII-I en_US
dc.subject VEGFR2 en_US
dc.subject p190RhoGAP en_US
dc.subject GATA2 en_US
dc.subject mechanotransduction en_US
dc.subject angiogenesis en_US
dc.subject capillary endothelial cell en_US
dc.title A Mechanosensitive Transcriptional Mechanism That Controls Angiogenesis en_US
dc.type Journal Article en_US
dc.description.version Accepted Manuscript en_US
dc.relation.journal Nature en_US
dash.depositing.author Ingber, Donald Elliott
dash.embargo.until 10000-01-01

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  • FAS Scholarly Articles [6948]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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