Kringle 1 of human hepatocyte growth factor inhibits bovine aortic endothelial cell proliferation stimulated by basic fibroblast growth factor and causes cell apoptosis.
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.
Xin
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Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, 320 Yue Yang Road, ShangHai, 200031, People's Republic of China.
Xu
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Zhang
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Li
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Gan
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D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D043168:Angiostatins; D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018082:Kringles; D010446:Peptide Fragments / Q000494:pharmacology; D010958:Plasminogen / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D016415:Sequence Alignment
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D043168:Angiostatins; D010958:Plasminogen