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.
Ramadori
G
G
Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany.
Neubauer
K
K
Odenthal
M
M
Nakamura
T
T
Knittel
T
T
Schwögler
S
S
Meyer zum Büschenfelde
K H
KH
D000199:Actins / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002469:Cell Separation; D002478:Cells, Cultured; D015342:DNA Probes; D015536:Down-Regulation; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D017228:Hepatocyte Growth Factor; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000199:Actins; D015342:DNA Probes; D005353:Fibronectins; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor