抄録
Hepatocyte growth factor (HGF), which is also known as a scatter factor or fibroblastderived tumor cytotoxic factor, is most likely a physiological hepatotrophic factor. Regulatory mechanisms for HGF gene expression are important in understanding the control of liver regeneration. Analysis of the 5'-flanking region of the HGF gene has revealed several putative regulatory elements found in inducible genes, but functional characterization of the elements largely remains to be determined. HGF is produced by fibroblasts, vascular smooth muscle cells, a variety of human leukemia cell lines and human mesangial cells in culture. Fibroblasts and leukemia cells have been used to examine the factors that regulate HGF gene expression. cAMP-elevating agents, such as cholera toxin, forskolin and prostaglandin E2, membrane-permeable cAMP analogues and ascorbic acid, as well as protein kinase C (PKC)-activating phorbol esters, interleukin 1 and tumor necrosis factor-a, markedly up-regulate HGF gene expression. A reporter plasmid containing the mouse HGF gene promoter is responsive to interleukin 6 stimulation in transfected NIH 3T3 cells. In addition, heparin increases production of HGF, but without any increase in HGF mRNA levels. HGF gene expression is downregulated by transforming growth factor-fl, dexamethasone and 1,25-dihydroxyvitamin D3- Thus, HGF gene expression is positively and negatively regulated by various cytokines and steroid hormones.
