Hepatocyte apoptosis and hepatic expression of transforming growth factor-β1 mRNA during involution of hyperplastic rat liver induced by hepatocyte growth factor |
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| Authors: | SUMIKO NAGOSHI HISATAKA YASUDA JYUN SUDA FUMIO YAMANOBE AKIHIKO OHNO KANJI HIGASHIO KENJI FUJIWARA |
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| Affiliation: | *First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Tochigi, Japan;†Third Department of Internal Medicine, Saitama Medical School, Saitama, Tochigi, Japan;‡Life Science Research Institute, Snow Brand Milk Products Co. Ltd, Tochigi, Japan |
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| 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)-β1 is reported to be expressed to stimulate hepatocyte apoptosis. In regenerating liver after partial resection showing no hyperplasia, such expression of TGF-β1 is also seen. However, no hepatocyte apoptosis develops despite the high levels of TGF-β1. 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-β1 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-β1 mRNA levels. |
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| Keywords: | hepatocyte apoptosis, hepatocyte growth factor, transforming growth factor-β1. |
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