Up-regulation of hepatocyte growth factor caused by an over-expression of transforming growth factor beta, in the rat model of fulminant hepatic failure.
BACKGROUND
The role of transforming growth factor beta (TGF-beta), a potent regulator of cellular growth, was investigated in the rat model of fulminant hepatic failure (FHF).


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-beta1 gene was performed by the systemic injection of AxCAhTGFb1 (1 x 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-beta1 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-alpha (24 h), compared to those in control Groups 2 and 3. Serum IL-6 levels were also elevated by a TGF-beta1 over-expression at 24 hrs after FHF in Group 1.


CONCLUSIONS
The forced expression of TGF-beta1 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-beta1 is thus thought to have an important role in inhibiting liver regeneration after FHF.
Nozato
Eiji
E
First Department of Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. k988749@med.u-ryukyu.ac.jp
Shiraishi
Masayuki
M
Nishimaki
Tadashi
T
D000256:Adenoviridae / Q000235:genetics; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005697:Galactosides; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D022781:Hepatocytes / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007211:Indoles; D017093:Liver Failure / Q000473:pathology* / Q000503:physiopathology*; D008115:Liver Regeneration; D008297:Male; D009336:Necrosis; D009929:Organ Size; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D016207:Cytokines; D005697:Galactosides; D007211:Indoles; D018809:Proliferating Cell Nuclear Antigen; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside