Up-regulation of hepatocyte growth factor caused by an over-expression of transforming growth factor β, in the rat model of fulminant hepatic failure

Abstract

Background The role of transforming growth factor β (TGF-β), a potent regulator of cellular growth, was investigated in the rat model of fulminant hepatic failure (FHF). Materials and methods The rat FHF model was created by a combination of a 68% partial hepatectomy (PH) and 7% of necrosis (each n = 25 in Groups 1, 2 and 3). Adenovirus mediated gene transfer of mature human TGF-β1 gene was performed by the systemic injection of AxCAhTGFb1 (1 × 10 9 pfu) in Group 1, 3 days before FHF. In control Groups 2 and 3, recombinant lacZ adenovirus (AxCAlacZ, Group 2) and normal saline (1 ml, Group 3) were used, instead of AxCAhTGFb1. Results An excessive expression of TGF-β1 in Group 1 resulted in an inhibition of hepatocyte proliferation (24–48 h after FHF) and gaining of liver weight (24–48 h), increased expression of HGF in liver tissue (24 h), and decreased expression of TGF-α (24 h), compared to those in control Groups 2 and 3. Serum IL-6 levels were also elevated by a TGF-β1 over-expression at 24 hrs after FHF in Group 1. Conclusions The forced expression of TGF-β1 in the FHF liver yields both a secondary increase of HGF production and a suppression of liver regeneration, which might explain the mechanism of increased serum HGF observed in a clinical FHF. TGF-β1 is thus thought to have an important role in inhibiting liver regeneration after FHF.