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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.
- Source :
-
Journal of hepatology [J Hepatol] 2002 May; Vol. 36 (5), pp. 637-44. - Publication Year :
- 2002
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Benzamidines pharmacology
Cell Division drug effects
Hepatectomy
Hepatocytes cytology
Male
Mice
Mice, Inbred BALB C
RNA, Messenger analysis
Serine Proteinase Inhibitors pharmacology
Transforming Growth Factor beta1
Liver Regeneration physiology
Matrix Metalloproteinase 2 genetics
Proto-Oncogene Proteins c-jun genetics
Transforming Growth Factor beta genetics
Urokinase-Type Plasminogen Activator antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0168-8278
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 11983447
- Full Text :
- https://doi.org/10.1016/s0168-8278(02)00024-7