title: After portal branch ligation in the rat, cellular proliferation is associated with selective induction of c-Ha-ras, p53, cyclin E, and Cdk2.
abstract: BACKGROUND
  In liver regeneration after portal branch ligation we previously showed that early cellular changes are observed in both the proliferating and atrophying liver lobes. They are therefore not indicative of future proliferative response. In this study we attempted to define precisely, in the same model, the time at which the cellular processes diverge between the lobes by measuring various parameters associated with cellular proliferation. We also investigated the possible role of inhibitors of cell proliferation in the absence of progression towards the S phase in the atrophying lobes.
  
  
  OBJECTIVE
  Expression of p53, c-Ha-ras, cyclin E, cyclin dependent kinase (Cdk2), transforming growth factor (TGF)-beta, and interleukin (IL)-1alpha and IL-1beta were assessed in relation to their potential role in proliferating and atrophying cellular phenomenons.
  
  
  METHODS
  Immunohistochemistry, northern blotting, western blotting, and reverse transcription-polymerase chain reaction were performed, mainly at time points corresponding to mid-G1/S phase progression (8-24 hours after surgery).
  
  
  RESULTS
  The common and thus most likely non-specific response was still evident 5-8 hours after surgery and included an increase in IL-1 mRNA as well as p53 and cyclin E proteins. From 12 hours onwards, p53, c-Ha-ras, cyclin E, and Cdk2 were selectively induced in proliferating lobes whereas IL-1beta was predominantly activated in atrophying lobes. No changes in TGF-beta or IL-1alpha expression were observed at the same time points in any of the liver lobes.
  
  
  CONCLUSIONS
  The initial response to portal branch ligation and thus probably to partial hepatectomy seems to be non-specific for at least eight hours. Thereafter, p53, c-Ha-ras, cyclin E, and Cdk2 seem to drive cellular proliferation while IL-1beta is associated with cellular atrophy. In contrast, TGF-beta and IL-1alpha do not seem to play a role in determining the commitment of cells towards atrophy or proliferation.
authors: Laboratories of Gastroenterology, Université Catholique de Louvain, 1200 Brussels, Belgium.
authors: P
authors: P
authors: Stärkel
authors: L
authors: L
authors: Lambotte
authors: C
authors: C
authors: Sempoux
authors: C
authors: C
authors: De Saeger
authors: A
authors: A
authors: Saliez
authors: D
authors: D
authors: Maiter
authors: Y
authors: Y
authors: Horsmans
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002455:Cell Division / Q000502:physiology; D019927:Cyclin E / Q000502:physiology*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D015870:Gene Expression; D016158:Genes, p53 / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D006498:Hepatectomy / Q000379:methods*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000502:physiology; D008026:Ligation; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D019927:Cyclin E; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases