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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Nomura
Kazuhiko
K
First Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Nagano, Matsumoto 390-8621, Japan.
Miyagawa
Shinichi
S
Ayukawa
Koichi
K
Soeda
Junpei
J
Taniguchi
Shun-ichiro
S
Kawasaki
Seiji
S
D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D001550:Benzamidines; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C006500:4-aminobenzamidine; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2