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Diaz-Gil JJ, Garcia-Monzon C, Rua C, Martin-Sanz P, Cereceda RM, Miquilena-Colina ME, Machin C, Fernandez-Martinez A, Garcia-Canero R: Liver growth factor antifibrotic activity in vivo is associated with a decrease in activation of hepatic stellate cells. J Cell Sci. 2009 Aug 1;122(Pt 15):2769-81. Epub 2009 Jul 13. 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. |
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