CHARACTERIZATION OF THE PROMOTER REGION OF THE RAT HEPATOCYTE-GROWTH-FACTOR SCATTER-FACTOR GENE

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen for hepatocytes in primary culture. In response to liver damage, the levels of HGF/SF mRNA change in various tissues. In this study, we isolated a genomic DNA fragment containing the promoter region of the rat HGF/SF gene and analyzed transcription-initiation sites and their utilization in response to acute liver injury. Rat HGF/SF-mRNA synthesis starts from at least three sites in the liver, spleen and kidney. One of these sites is preferentially utilized in the liver and spleen in response to acute liver injury. In the 5' flanking region, several cytokine-related sequence elements that might be involved in the regulation of HGF/SF-gene expression are located near the transcription-initiation sites. The effects of cytokines related to these sequence elements on the production of HGF/SF mRNA were examined using a cell culture system. Transforming growth factor-beta1 (TGF-beta1) inhibits the production of HGF/SF mRNA by Shay granulocytic sarcoma-derived cells. The TGF-beta1-inhibitory element, one of the sequence elements present in the promoter sequence, may mediate the inhibition of HGF/SF-gene expression by TGF-beta1.