Liver growth factor antifibrotic activity in vivo is associated with a decrease in activation of hepatic stellate cells.
The antifibrotic activity of Liver Growth Factor (LGF), a liver mitogen, was previously demonstrated in several models of rat liver fibrosis and even in extrahepatic sites, such as carotid artery in hypertensive rats and rat CdCl2-induced lung fibrosis. In the present study, we have attempted to examine in depth its mechanism of antifibrotic action in bile duct-ligated (BDL) rats, with special emphasis on its activity in fibrogenic liver cells. BDL rats received either LGF 9 microg/week for 2 or 3 weeks (BDL+LGF, n=20/group) or saline (BDL+S, n=20/group), at times 0, week 2, or week 5 after operation. Groups were compared in terms of liver alpha-smooth muscle actin (SMA) content (western blotting and immunohistochemistry), hepatic apoptosis, liver desmin content (western blotting), and serum endothelin-1 (ELISA). LGF produced a marked decrease in liver alpha-SMA content compared with saline-injected rats, especially evident at longer times (5w and 8w; p<0.05). Moreover, LGF did not seem to influence HSC proliferation, as shown by measuring liver desmin content. The antifibrotic activity exerted by LGF seems to be closely related to a modulation of the activation state of fibrogenic liver cells (activated HSC and myofibroblasts) in BDL rats.
Díaz-Gil
Juan J
JJ
Department of Experimental Biochemistry, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. jdiaz.hpth@salud.madrid.org
García-Monzón
Carmelo
C
Rúa
Carmen
C
Martín-Sanz
Paloma
P
Cereceda
Rosa M
RM
Miquilena-Colina
María E
ME
Machín
Celia
C
Fernández-Martínez
Amalia
A
García-Cañero
Rafael
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001652:Bile Ducts; D001663:Bilirubin / Q000378:metabolism* / Q000494:pharmacology; D003893:Desmin / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism* / Q000494:pharmacology; D000075462:Serum Albumin, Human; D013997:Time Factors
D000199:Actins; D001663:Bilirubin; D003893:Desmin; D019332:Endothelin-1; D012709:Serum Albumin; D000075462:Serum Albumin, Human; C053498:albumin-bilirubin complex; C498862:Acta2 protein, rat