Stimulation of liver growth by exogenous human hepatocyte growth factor in normal and partially hepatectomized rats

Human hepatocyte growth factor stimulates DNA synthesis by cultured rat hepatocytes. When human hepatocyte growth factor prepared from the culture medium of human embryonic lung fibroblasts was intravenously injected into normal rats and rats after 70% hepatectomy, it was detected in hepatocytes but not in nonparenchymal cells isolated 30 min after injection. Similar injections of human hepatocyte growth factor at 2-hr intervals for 10 hr significantly increased hepatic DNA content in normal rats at 48 hr, with increased hepatic content of putrescine, the essential polyamine for hepatic DNA synthesis after 70% hepatectomy, and activities of catalytic enzymes of putrescine synthesis at 6 hr almost to the levels in rats after 70% hepatectomy. Those levels in rats after 70% hepatectomy were further enhanced by similar injections of human hepatocyte growth factor starting immediately after surgery. Increased hepatic DNA content in normal rats and rats after 70% hepatectomy was also seen with recombinant human hepatocyte growth factor to a greater extent compared with that seen with human hepatocyte growth factor. In normal rats given recombinant human hepatocyte growth factor, 5-bromo-2'-deoxyuridine-labeled and mitotic hepatocytes were significantly increased in number at 26 hr but not at 48 hr. We conclude that exogenous human hepatocyte growth factor acts as a trigger and a promoter of liver growth to increase hepatic putrescine production in rats. Recombinant human hepatocyte growth factor is more potent than human hepatocyte growth factor in this action.