Hepatoprotective action of adenovirus-transferred HNF-3gamma gene in acute liver injury caused by CCl(4).

Hepatocyte nuclear factor-3gamma (HNF-3gamma) is an important regulator of liver-specific genes and the expression of this factor is reduced in the liver injured by carbon tetrachloride (CCl(4)). Wistar rats were infected with a recombinant adenovirus carrying the cDNA for HNF-3gamma (AxCAHNF3gamma) via the tail vein and were treated with CCl(4) by intraperitoneal injection. Liver damage, such as swelling of the hepatocytes and increases in serum marker enzymes were markedly alleviated by AxCAHNF3gamma infection. Interestingly, hepatocyte growth factor (HGF) was strongly induced in the AxCAHNF3gamma-infected liver. Likewise, HNF-1alpha and HNF-1beta levels were increased, but HNF-3alpha and HNF-3beta levels were depressed in the liver. Our results suggest that the transduced HNF-3gamma gene leads to a hepatoprotective effect via the induction of HGF by the combined actions of liver-enriched transcription factors.