Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride.

Abstract

Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen supposed to be a main stimulant of hepatocyte replication during liver regeneration. During acute liver injury, HGF has been detected in nonparenchymal cells of the liver. We performed in situ hybridization of HGF in rat livers after administration of carbon tetrachloride (CCl4). Mononuclear phagocytes (MNP) were isolated from normal and injured livers and HGF expression was analyzed by Northern blotting, in situ hybridization, and immunoprecipitation of 35S-labeled proteins. In situ hybridization of normal liver revealed few HGF positive cells within hepatic sinusoids. In injured livers, the number of cells containing HGF transcripts was increased at 6-24 h after CCl4. Hepatocyte growth factor transcripts in MNP from normal liver were detectable in trace amounts, but became clearly detectable at 6 h and persisted up to 24 h after CCl4 administration. In situ hybridization of MNP isolated from normal liver did not reveal positive cells. Mononuclear phagocytes became HGF-positive when isolated 6 h after CCl4. Hepatocyte growth factor protein was detected in MNP isolated 24 h after CCl4. Hepatocyte growth factor in MNP is not directly induced by interferon-alpha, interferon-gamma or tumour necrosis factor-alpha (TNF-alpha). Stimulated resident mononuclear phagocytes may play a significant role in the increase of HGF expression in liver regeneration after acute liver injury.