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

J Hepatol. 2002 May;36(5):637-44. doi: 10.1016/s0168-8278(02)00024-7.

Abstract

Background/aims: 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.

MeSH terms

  • 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*

Substances

  • Benzamidines
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Serine Proteinase Inhibitors
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • 4-aminobenzamidine
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinase 2