Impaired liver regeneration after partial hepatectomy in plasminogen deficient mice

Liver regeneration is regulated by variety of growth factors. Release and a ctivation of these growth factors are deeply related to degradation of extr acellular matrix (ECM), which is regulated by plasminogen-activating system . Since plasminogen is assumed to be essential in these functions in liver regeneration, partial 70% hepatectomy (PH) was performed on plasminogen def icient (Pig-/-) mice and wild-type (Pig+/+) mice. The sequential recovery o f the liver weight after 70% PH gradually increased over 1 to 14 days in Pi g+/+ mice. However, in Pig-/- mice, it increased over 1 to 7 days and there after increased no more. Thus, the recovery in Pig-/- mice was significantl y impaired at 10 and 14 days compared with Pig+/+ mice. Pig+/+ mice exhibit ed an increase in DNA synthesis over 5 days, and then a decrease thereafter ; however, in Pig-/- mice, it increased over 3 days, and decreased thereaft er, with the significant decrease at 14 days. The apoptotic nuclei labellin g index slightly increased over 3 days, and decreased thereafter in Pig+/mice. In Pig-/- mice, it was few detected over 3 days, and gradually increa sed over 7 to 14 days. The apoptotic index in Pig -/- mice was higher than Pig +/+ mice at 14 days. In the histological examination of liver, focal ar ea of cellular loss with fibrin deposition were detected in Pig-/- mice aft er PH, which were rarely detected in Pig+/+ mice. In Pig-/- mice, expressio ns of t-PA, u-PA and pro-MMP-9 were increased in the liver at 14 days after PH compared with Pig+/+ mice. These findings suggest that plasminogen play s an important role in liver regeneration after PH. (C) 2001 Harcourt Publi shers Ltd.