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.


OBJECTIVE
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 3h 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.
Mueller
Lars
L
Department of Hepato-biliary Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. l.mueller@uke.uni-hamburg.de
Broering
Dieter C
DC
Meyer
Jannine
J
Vashist
Yogesh
Y
Goettsche
Juliane
J
Wilms
Christian
C
Rogiers
Xavier
X
D000818:Animals; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology; D006498:Hepatectomy; D006657:Histones / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics; D008099:Liver / Q000098:blood supply / Q000502:physiology / Q000601:surgery; D008102:Liver Circulation / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D023421:Models, Animal; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011169:Portal Vein / Q000502:physiology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C486110:Egr1 protein, rat; D006657:Histones; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014157:Transcription Factors; C490198:PTP4A1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C490199:Ptp4a1 protein, rat