Activated rat stellate cells express c-met and respond to hepatocyte growth factor to enhance transforming growth factor beta1 expression and DNA synthesis.
Hepatocyte growth factor (HGF) decreases transforming growth factor beta1 (TGFbeta1) levels in the liver and attenuates hepatic fibrosis caused by dimethylnitrosamine in rats. In the liver, HGF is presumed to act predominantly on parenchymal cells, and TGFbeta1 is produced mainly by mesenchymal cells. In hepatic fibrosis, stellate cells play a central role with undergoing activation, which also occurs when the cells are cultured on plastic. Thus, we wondered if HGF could act directly on stellate cells. c-Met was detected in rat stellate cells activated by culture for 10 days, but not in the cells cultured for 3 days. Specific binding of HGF to the activated cells was determined, and Scatchard analysis indicated an apparent Kd of 1.5 nM. c-Met mRNA was detected in freshly isolated stellate cells from rats treated with carbon tetrachloride for 8 weeks, but not in those cells from normal rats. These results indicate that stellate cells express c-met when activated in vitro and in vivo. HGF enhanced TGFbeta1 production and DNA synthesis in the activated cells.
Ikeda
H
H
First Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Nagoshi
S
S
Ohno
A
A
Yanase
M
M
Maekawa
H
H
Fujiwara
K
K
D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met