PMID- 11983447 OWN - NLM STAT- MEDLINE DCOM- 20021213 LR - 20190817 IS - 0168-8278 (Print) IS - 0168-8278 (Linking) VI - 36 IP - 5 DP - 2002 May TI - 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. PG - 637-44 AB - 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. FAU - Nomura, Kazuhiko AU - Nomura K AD - First Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Nagano, Matsumoto 390-8621, Japan. FAU - Miyagawa, Shinichi AU - Miyagawa S FAU - Ayukawa, Koichi AU - Ayukawa K FAU - Soeda, Junpei AU - Soeda J FAU - Taniguchi, Shun-ichiro AU - Taniguchi S FAU - Kawasaki, Seiji AU - Kawasaki S LA - eng PT - Journal Article PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 0 (Benzamidines) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (RNA, Messenger) RN - 0 (Serine Proteinase Inhibitors) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 63GK9KT599 (4-aminobenzamidine) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Animals MH - Benzamidines/pharmacology MH - Cell Division/drug effects MH - Hepatectomy MH - Hepatocytes/cytology MH - Liver Regeneration/*physiology MH - Male MH - Matrix Metalloproteinase 2/*genetics MH - Mice MH - Mice, Inbred BALB C MH - Proto-Oncogene Proteins c-jun/*genetics MH - RNA, Messenger/analysis MH - Serine Proteinase Inhibitors/pharmacology MH - Transforming Growth Factor beta/*genetics MH - Transforming Growth Factor beta1 MH - Urokinase-Type Plasminogen Activator/*antagonists & inhibitors EDAT- 2002/05/02 10:00 MHDA- 2002/12/17 04:00 CRDT- 2002/05/02 10:00 PHST- 2002/05/02 10:00 [pubmed] PHST- 2002/12/17 04:00 [medline] PHST- 2002/05/02 10:00 [entrez] AID - S0168827802000247 [pii] AID - 10.1016/s0168-8278(02)00024-7 [doi] PST - ppublish SO - J Hepatol. 2002 May;36(5):637-44. doi: 10.1016/s0168-8278(02)00024-7.