title: Hepatocyte apoptosis and hepatic expression of transforming growth factor-beta1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nagoshi
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: J
authors.initials: J
authors.lastname: Suda
authors.forename: F
authors.initials: F
authors.lastname: Yamanobe
authors.forename: A
authors.initials: A
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Higashio
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis; D004247:DNA / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D004247:DNA