Inhibition of urokinase-type plasminogen activator delays expression of c-jun, activated transforming growth factor β1, and matrix metalloproteinase 2 during post-hepatectomy liver regeneration in mice

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 β1 (TGF-β1), 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-β1 expression, and expression of MMP-2 activity, were 2 h, 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.