Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors.
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.
Gandhi
Chandrashekhar R
CR
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, E-1540 BST, 200 Lothrop Street, Pittsburgh, PA 15213, USA. gandhics@msx.upmc.edu
Murase
Noriko
N
Subbotin
Vladimir M
VM
Uemura
Tadahiro
T
Nalesnik
Michael
M
Demetris
Anthony J
AJ
Fung
John J
JJ
Starzl
Thomas E
TE
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
D006133:Growth Substances; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta