Abstract
The Kruppel-like factor KLF2 was recently identified as a novel regulator of endothelial pro-inflammatory and pro-thrombotic function. Here it is shown that overexpression of KLF2 potently inhibits vascular permeability factor/vascular endothelial growth factor (VEGF-A)-mediated angiogenesis and tissue edema in the nude ear mouse model of angiogenesis. In vitro, KLF2 expression retards VEGF-mediated calcium flux, proliferation and induction of pro-inflammatory factors in endothelial cells. This effect is due to a potent inhibition of VEGFR2/KDR expression and promoter activity. These observations identify KLF2 as a regulator of VEGFR2/KDR and provide a foundation for novel approaches to regulate angiogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Animals
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Blotting, Western
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Calcium / metabolism
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Cell Nucleus / metabolism
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Cell Proliferation
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Cells, Cultured
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Endothelium, Vascular / cytology
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Green Fluorescent Proteins / metabolism
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Humans
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Inflammation
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Kruppel-Like Transcription Factors
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Male
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Mice
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Mice, Nude
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Neovascularization, Pathologic*
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Thrombosis
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Time Factors
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Trans-Activators / metabolism*
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Transfection
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Vascular Endothelial Growth Factor A / antagonists & inhibitors*
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Zinc Fingers
Substances
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KLF2 protein, human
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Klf2 protein, mouse
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Kruppel-Like Transcription Factors
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Trans-Activators
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Vascular Endothelial Growth Factor A
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Green Fluorescent Proteins
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Calcium