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Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

Gandhi, CR and Murase, N and Subbotin, VM and Uemura, T and Nalesnik, M and Demetris, AJ and Fung, JJ and Starzl, TE (2002) Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors. Journal of Hepatology, 37 (3). 340 - 348. ISSN 0168-8278

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Abstract

Background/Aims: 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)-β, 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-β concentration that peaked at 1.4 × baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-α 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-β concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-β constrains the amount of hepatocyte proliferation independently from control of liver volume. © 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gandhi, CR
Murase, N
Subbotin, VM
Uemura, T
Nalesnik, Mnalesnik@pitt.eduNALESNIK
Demetris, AJ
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 September 2002
Date Type: Publication
Journal or Publication Title: Journal of Hepatology
Volume: 37
Number: 3
Page Range: 340 - 348
DOI or Unique Handle: 10.1016/s0168-8278(02)00165-4
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0168-8278
Other ID: uls-drl:31735062120815, Starzl CV No. 2175
Date Deposited: 08 Apr 2010 17:37
Last Modified: 27 Jan 2019 02:55
URI: http://d-scholarship.pitt.edu/id/eprint/5561

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