Resumen de Liver growth factor antifibrotic activity in vivo is associated with a decrease in activation of hepatic stellate cells

J.J Diaz Gil, Carmelo García Monzón, Paloma Martín Sanz, Celia Machin, Amalia Fernández Martínez, María del Carmen Rúa Rodríguez, Rosa M. Cereceda, María E. Miquilena-Colina, Rafael García-Cañero

• 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 µg/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 a-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 ?-SMA content compared with saline-injected rats, especially evident at longer times (5w and 8w; p<0.05), accompanied by a decrease in hepatic ?-SMA+ cells. This decrease was not due to the killing of activated hepatic stellate cells (HSC) or myofibroblasts by LGF, since there was a slight decrease in hepatic apoptosis that was more evident at 2w (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.