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

• Published in: The Journal of surgical research Vol. 115; no. 2; pp. 226 - 234
• Main Authors: Nozato, Eiji, Shiraishi, Masayuki, Nishimaki, Tadashi
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-2003; Elsevier
• Subjects: Adenoviridae - genetics; Alanine Transaminase - blood; Animals; Apoptosis - physiology; Aspartate Aminotransferases - blood; Biological and medical sciences; Body Weight; Cytokines - blood; Disease Models, Animal; fulminant hepatic failure; Galactosides; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression; Gene Transfer Techniques; hepatocyte growth factor; Hepatocyte Growth Factor - genetics; Hepatocytes - chemistry; Hepatocytes - pathology; Hepatocytes - physiology; In Situ Nick-End Labeling; In Vitro Techniques; Indoles; interluekin-6; Liver Failure - pathology; Liver Failure - physiopathology; Liver Regeneration; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Necrosis; Organ Size; Other diseases. Semiology; Proliferating Cell Nuclear Antigen - analysis; Rats; Rats, Wistar; regeneration; Staining and Labeling; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1; transforming growth factor β; Up-Regulation; interluekin-6; necrosis; regeneration; fulminant hepatic failure; transforming growth factor β; hepatocyte growth factor; Rat; Hepatocyte growth factor; Transforming growth factor β; Liver; Rodentia; Cell biology; Hepatic disease; Fulminant; Regeneration; Vertebrata; Liver failure; Experimental disease; Regulation(control); Mammalia; Animal; Digestive diseases; Mechanism of action
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/S0022-4804(03)00316-0

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).
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.
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.
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.