Hepatocyte apoptosis and hepatic expression of transforming growth factor-beta1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor.

Hepatocyte apoptosis occurs during involution of hyperplastic liver induced by administration of xenobiotic compounds in rats. With this hyperplasia and involution, hepatic transforming growth factor (TGF)-beta1 is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-beta1 is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-beta1. When rats received an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h after the last injection to 140% of control. This DNA content was significantly decreased at 108 and 180 h after discontinuation of treatment. At 60 h after the last injection, the number of apoptotic bodies positive for nick end-labelling of DNA in hepatocytes was significantly greater in treated rats than in control rats. Hepatocyte apoptosis was also identified electron micrographically. Hepatic TGF-beta1 mRNA levels in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude that hyperplastic liver induced in normal rats by hepatocyte growth factor regresses with hepatocyte apoptosis and suppressed hepatic TGF-beta1 mRNA levels.