Inhibition of urokinase-type plasminogen activator delays expression of c-jun, activated transforming growth factor beta 1, and matrix metalloproteinase 2 during post-hepatectomy liver regeneration in mice

• Published in: Journal of hepatology 2002-05, Vol.36 (5), p.637-644
• Main Authors: Nomura, Kazuhiko, Miyagawa, Shinichi, Ayukawa, Koichi, Soeda, Junpei, Taniguchi, Shun-ichiro, Kawasaki, Seiji
• Format: Article
• Language: English
• Subjects: Animals; Benzamidines - pharmacology; Cell Division - drug effects; Hepatectomy; Hepatocytes - cytology; Liver Regeneration - physiology; Male; Matrix Metalloproteinase 2 - genetics; Mice; Mice, Inbred BALB C; Proto-Oncogene Proteins c-jun - genetics; RNA, Messenger - analysis; Serine Proteinase Inhibitors - pharmacology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1; Urokinase-Type Plasminogen Activator - antagonists & inhibitors
• ISSN: 0168-8278
• DOI: 10.1016/S0168-8278(02)00024-7

Although urokinase-type plasminogen activator (u-PA) is suggested to initiate various factors in liver regeneration after hepatectomy, no corroborative evidence has been reported. In the present study, we investigated the effect of u-PA on liver regeneration after hepatectomy. Mice were placed into either a control group or a u-PA-inhibited group that received an in vivo u-PA inhibitor, p-aminobenzamidine. After we had removed two-thirds of the liver, we examined the expressions of c-jun mRNA and activated transforming growth factor beta 1 (TGF-beta 1), matrix metalloproteinase-2 (MMP-2) activity, and the level of hepatocyte and non-parenchymal cell proliferation in the two groups. In the u-PA-inhibited group, the delays in c-jun mRNA expression, hepatocyte proliferation, activated TGF-1 expression, and expression of MMP-2 activity, were 2h, 1, 2, and 1 day, respectively, and the sinusoid architecture was not restored by 10 days after hepatectomy. u-PA inhibition delays the expression of c-jun mRNA, hepatocyte proliferation, and restoration of the sinusoid architecture, suggesting that u-PA plays important roles in liver regeneration after hepatectomy through control of a transcription factor, c-jun expression.