Expression of activin A is increased in cirrhotic and fibrotic rat livers.
OBJECTIVE
Activin A, a member of the transforming growth factor (TGF)-beta superfamily, recently has been reported to suppress DNA synthesis and to induce apoptosis of hepatocytes. These biological functions are similar to those of TGF-beta1, which is overexpressed in liver cirrhosis. The aim of this study was to examine whether activin A is involved in liver cirrhosis and fibrosis.


METHODS
Liver cirrhosis or fibrosis was induced by intraperitoneal injections of dimethylnitrosamine or porcine serum into rats. The kinetics of activin A messenger RNA (mRNA) expression in cirrhotic and fibrotic livers and primary cultured rat hepatocytes were assessed by Northern blotting, and the localization of activin A was determined immunohistochemically. Modulation of type 1 collagen mRNA expression by activin A in rat cultured Ito/fat-storing cells and fibroblasts was also examined.


RESULTS
Northern blotting showed that activin A mRNA expression was enhanced in fibrotic livers. The numbers of hepatocytes expressing immunoreactive activin A were significantly greater, especially around the fibrotic areas. Activin A mRNA expression in cultured hepatocytes was increased significantly by TGF-beta1 and by activin A itself. Furthermore, type 1 collagen mRNA expression in cultured cells was enhanced by activin A and TGF-beta1 in a synergistic manner.


CONCLUSIONS
Activin A is overexpressed in rat cirrhotic and fibrotic livers and may contribute to hepatic fibrogenesis.
Sugiyama
M
M
Department of Internal Medicine III, Niigata University School of Medicine, Niigata City, Japan.
Ichida
T
T
Sato
T
T
Ishikawa
T
T
Matsuda
Y
Y
Asakura
H
H
D028341:Activins; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D007265:Inhibins / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D003094:Collagen; D004247:DNA