抄録
Hepatocyte growth factor (HGF) was originally identified as a potent growthpromoting factor for rat hepatocytes in primary culture. Recent progress, however, has revealed that HGF is mitogenic to some epithelial cells other than hepatocytes and to endothelial cells. It is also a multifunctional cytokine with mitogenic, motogenic, morphogenic and tumor-suppressing activities. Despite its broad-spectrum of biological activities, HGF is most likely the physiological hepatotrophic factor that triggers or modulates liver regeneration. HGF levels in plasma and liver of experimental animals, partially hepatectomized or treated with hepatotoxins, increase prior to induction of hepatic DNA synthesis. In this review, we focus upon regulation of gene expression and production of HGF by cultured fibroblasts and other cells. Human HGF (hHGF) mRNA expression is upregulated by interleukin-1, probably via the nuclear factor-interleukin-6binding element located near the transcription initiation site of the hHGF gene. Tumor necrosis factor-a, and activators of protein kinase C stimulate HGF gene expression and production of HGF. Injurin, a heat-stable protein found in sera of rats that have undergone injury of the liver or kidney, also induces HGF mRNA expression, although its physicochemical and biological properties are only partially characterized. Dexamethasone and transforming growth factor-fl inhibit gene expression and production of HGF. The effects of the latter are more potent than those of the former. The physiological significance of the stimulators and inhibitors of HGF production is discussed.
