A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 2009 Feb 26;457(7233):1103-8
Date
02/27/2009Pubmed ID
19242469Pubmed Central ID
PMC2708674DOI
10.1038/nature07765Scopus ID
2-s2.0-61349168351 (requires institutional sign-in at Scopus site) 434 CitationsAbstract
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.
Author List
Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DEAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Cell Line
Endothelial Cells
Endothelium, Vascular
Extracellular Matrix
GATA2 Transcription Factor
Gene Knockdown Techniques
Guanine Nucleotide Exchange Factors
Humans
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic
Repressor Proteins
Retinal Vessels
Signal Transduction
Transcription Factors
Transcription Factors, TFII
Transcription, Genetic
Up-Regulation
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
