title: Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors.
abstract: OBJECTIVE
  The response to the liver damage caused by portacaval shunt (PCS) is characterized by low-grade hyperplasia and atrophy. To clarify mechanisms of this dissociation, we correlated the expression of 'hepatotrophic factors' and the antihepatotrophic and proapoptotic peptide, transforming growth factor (TGF)-beta, with the pathologic changes caused by PCS in rats.
  
  
  METHODS
  PCS was created by side-to-side anastomosis between the portal vein and inferior vena cava, with ligation of the hilar portal vein. Hepatic growth mediators were measured to 2 months.
  
  
  RESULTS
  The decrease in the liver/body weight ratio during the first 7 days which stabilized by day 15, corresponded to parenchymal cell apoptosis and increases in hepatic TGF-beta concentration that peaked at 1.4 x baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-alpha and augmenter of liver regeneration) also occurred during the period of hepatocellular apoptosis.
  
  
  CONCLUSIONS
  The development of hepatic atrophy was associated with changes in TGF-beta concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-beta constrains the amount of hepatocyte proliferation independently from control of liver volume.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, E-1540 BST, 200 Lothrop Street, Pittsburgh, PA 15213, USA. gandhics@msx.upmc.edu
authors.forename: Chandrashekhar R
authors.initials: CR
authors.lastname: Gandhi
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Subbotin
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Uemura
authors.forename: Michael
authors.initials: M
authors.lastname: Nalesnik
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000818:Animals; D017209:Apoptosis; D001284:Atrophy; D002455:Cell Division; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006499:Hepatic Artery / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D006133:Growth Substances; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta