Impaired liver regeneration after partial hepatectomy in plasminogen deficient mice

Abstract

Liver regeneration is regulated by variety of growth factors. Release and activation of these growth factors are deeply related to degradation of extracellular matrix (ECM), which is regulated by plasminogen-activating system. Since plasminogen is assum ed to be essential in these functions in liver regeneration, partial 70% hepatectomy (PH) was performed on plasminogen deficient (Plg−/−) mice and wild-type (Plg+/+) mice. The sequential recovery of the liver weight after 70% PH gradually increased over 1 to 14 days in Plg+/+ mice. However, in Plg−/− mice, it increased over 1 to 7 days and thereafter increased no more. Thus, the recovery in Plg−/− mice was significantly impaired at 10 and 14 days compared with Plg+/+ mice. Plg+/+ mice exhibited an increase in DNA synthesis over5 days, and then a decrease thereafter; however, in Plg−/− mice, it increased over 3 days, and decreased thereafter, with the significant decrease at 14 days. The apoptotic nuclei labelling index slightly increased over 3 days, and decreased thereafter in Plg+/+ mice. In Plg−/− mice, it was few detected over 3 days, and gradually increased over 7 to 14 days. The apoptotic index in Plg−/− mice was higher than Plg+/+ mice at 14 days. In the histological examination of liver, focal area of cellular loss with fibrin deposition were detected in Plg−/− mice after PH, which were rarely detected in Plg+/+ mice. In Plg−/− mice, expressions of t-PA, u-PA and pro-MMP-9 were increased in the liver at 14 days after PH compared with Plg+/+ mice. These findings suggest that plasminogen plays an important role in liver regeneration after PH.