The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow

Background: The environmental triggers which control liver regeneration following partial hepatectomy (PH) are not clear. With respect to haemodynamic changes, the model of rat portal branch ligation (PBL) provides the unique opportunity to discriminate transcriptional events, which selectively result from increased portal flow. Aims: The potential role of portal over-flow on early expression of early growth response gene-1 (Egr-1), type-1 plasminogen activator inhibitor (PAI-1) and phosphatase of regenerating liver-1 (PRL-1) was analysed by a comparative experimental study using PBL and PH. Methods: Operative procedures were carried out in male Wistar rats. Growth kinetics were measured by liver weight indices. S-phase-specific mRNA-levels of H2B-histone protein (H2B), as well as expression analysis of Egr-1, PAI-1 and PRL-1 were examined by Northern blot experiments. Results: Growth patterns did not differ significantly between PBL and PH, whereas peak H2B expression occurred earlier after PH. Egr-1 and PAI-1 were specifically induced during the first few hours in the hyper-perfused lobes following PBL and PH. PRL-1-expression selectively peaked 3 h after PH and PBL in the hyper-perfused lobes. Conclusions: Increased portal flow after PBL and PH was associated with induction of Egr-1, PAI-1 and PRL-1. Thus, haemodynamic changes affect the molecular immediate-early response during liver regeneration. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.