The gene of hepatocyte growth factor is expressed in fat-storing cells of rat liver and is downregulated during cell growth and by transforming growth factor-beta.

Hepatocyte growth factor (HGF) has been detected in non-parenchymal cells but not in hepatocytes. We performed Northern blot analysis of total RNA extracted from rat hepatocytes, Kupffer cells, endothelial cells and fat-storing (Ito-) cells. Total RNA was extracted from fat-storing cells at different times after isolation and from cells treated with different amounts of transforming growth factor beta. The RNA was hybridized with HGF, fibronectin-, and alpha-actin-specific cDNA probes, consecutively. We found an abundant amount of HGF mRNA in freshly isolated fat-storing cells, but not in other liver cells. The amount of the HGF transcripts decreases significantly in FSC during the time of culture, while fibronectin gene expression increases and alpha-actin gene expression as well. TGF-beta dramatically inhibits HGF gene expression, but causes an enhanced fibronectin mRNA level. Northern blot hybridisation of total RNA from CCl4-chronically damaged liver with HGF cDNA shows a significant increase of HGF mRNA during development of liver fibrosis. We suggest that in damaged liver either non-parenchymal cells, others than FSC, became able to express the HGF in vivo, or other mediators overcome the inhibitory effect of TGF-beta.