Liver growth factor antifibrotic activity in vivo is associated with a decrease in activation of hepatic stellate cells
- Autores: 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
- Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 24, Nº. 4, 2009, págs. 473-479
- Idioma: inglés
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Resumen
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.
