Abstract
Hepatocyte growth factor (HGF), also known as scatter factor, is a mesenchymal or stromal-derived mediator with angiogenic activity. There are four kringle domains in its amino terminus. They display considerable sequence similarity with those of angiostatin, an angiogenesis inhibitor. We now describe that the recombinant kringle1 of HGF (HGFK1) inhibits bovine aortic endothelial (BAE) cell proliferation stimulated by basic fibroblast growth factor in a dose-dependent manner, with an ED(50) of approximately 0.7 microg/ml, while ED(50) of angiostatin is 3 microg/ml. Treatment of BAE cell with HGFK1 caused cell apoptosis. This report thus constitutes the first demonstration that kringle1 of HGF is a selective inhibitor for BAE cell proliferation stimulated by bFGF.
Copyright 2000 Academic Press.
MeSH terms
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Angiostatins
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Animals
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Aorta / cytology*
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Aorta / drug effects
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Apoptosis / drug effects*
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Cattle
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Cell Division / drug effects
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Dose-Response Relationship, Drug
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Electrophoresis, Polyacrylamide Gel
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Fibroblast Growth Factor 2 / antagonists & inhibitors*
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Fibroblast Growth Factor 2 / pharmacology
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Hepatocyte Growth Factor / chemistry
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Hepatocyte Growth Factor / pharmacology*
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Humans
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Kringles*
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Peptide Fragments / pharmacology
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Plasminogen / chemistry
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Plasminogen / pharmacology
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Recombinant Proteins / chemistry
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Recombinant Proteins / pharmacology
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Sequence Alignment
Substances
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Angiogenesis Inhibitors
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Peptide Fragments
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Recombinant Proteins
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Fibroblast Growth Factor 2
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Hepatocyte Growth Factor
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Angiostatins
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Plasminogen