HEPATOCYTE APOPTOSIS AND HEPATIC EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA(1) MESSENGER-RNA DURING INVOLUTION OF HYPERPLASTIC RAT-LIVERINDUCED BY HEPATOCYTE GROWTH-FACTOR

Hepatocyte apoptosis occurs during involution of hyperplastic liver in duced by administration of xenobiotic compounds in rats. With this hyp erplasia and involution, hepatic transforming growth factor (TGF)-beta (1) is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, suc h expression of TGF-beta(1) is also seen. However, no hepatocyte apopt osis develops despite the high levels of TGF-beta(1). When rats receiv ed an intravenous injection of human hepatocyte growth factor at 12 h intervals for 14 days, the hepatic DNA content was increased 12 h afte r the last injection to 140% of control. This DNA content was signific antly decreased at 108 and 180 h after discontinuation of treatment. A t 60 h after the last injection, the number of apoptotic bodies positi ve for nick end-labelling of DNA in hepatocytes was significantly grea ter in treated rats than in control rats. Hepatocyte apoptosis was als o identified electron micrographically. Hepatic TGF-beta(1) mRNA level s in treated rats were significantly lower than in control rats at 12 h and then gradually increased towards control levels. We conclude tha t hyperplastic liver induced in normal rats by hepatocyte growth facto r regresses with hepatocyte apoptosis and suppressed hepatic TGF-beta 1 mRNA levels.