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 ED₅₀ of approximately 0.7 μg/ml, while ED₅₀ of angiostatin is 3 μg/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. (C) 2000 Academic Press.