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Rat liver myofibroblasts and hepatic stellate cells differ in CD95-mediated apoptosis and response to TNF-α

Rat liver myofibroblasts and hepatic stellate cells differ in CD95-mediated apoptosis and... Abstract Hepatic stellate cells (HSC), particularly activated HSC, are thought to be the principle matrix-producing cell of the diseased liver. However, other cell types of the fibroblast lineage, especially the rat liver myofibroblasts (rMF), also have fibrogenic potential. A major difference between the two cell types is the different life span under culture conditions. Although nearly no spontaneous apoptosis could be shown in rMF cultures, 18 ± 2% of the activated HSC ( day 7 ) were apoptotic. Compared with activated HSC, CD95R was expressed in 70% higher amounts in rMF. CD95L could only be detected in activated HSC. Stimulation of the CD95 system by agonistic antibodies (1 ng/ml) led to apoptosis of all rMF within 2 h, whereas activated HSC were more resistant (5.3 h/ 40% of total cells). Although transforming growth factor-β downregulated apoptosis in both activated HSC and rMF, tumor necrosis factor-α (TNF-α) upregulated apoptosis in rMF. Lack of spontaneous apoptosis and CD95L expression in rMF and the different reaction on TNF-α stimulation reveal that activated HSC and rMF belong to different cell populations. CD95 receptor CD95 ligand transforming growth factor-β Footnotes This study was supported by the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 402 Molekulare und Zelluläre Hepatogastroenterologie, project C6. Address for reprint requests and other correspondence: G. Ramadori, Dept. of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg August University Göttingen, Robert Koch Straße 40, 37075 Göttingen, Germany (E-mail: [email protected] ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. December 5, 2001;10.1152/ajpgi.00441.2001 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

Rat liver myofibroblasts and hepatic stellate cells differ in CD95-mediated apoptosis and response to TNF-α

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00441.2001
pmid
12121892
Publisher site
See Article on Publisher Site

Abstract

Abstract Hepatic stellate cells (HSC), particularly activated HSC, are thought to be the principle matrix-producing cell of the diseased liver. However, other cell types of the fibroblast lineage, especially the rat liver myofibroblasts (rMF), also have fibrogenic potential. A major difference between the two cell types is the different life span under culture conditions. Although nearly no spontaneous apoptosis could be shown in rMF cultures, 18 ± 2% of the activated HSC ( day 7 ) were apoptotic. Compared with activated HSC, CD95R was expressed in 70% higher amounts in rMF. CD95L could only be detected in activated HSC. Stimulation of the CD95 system by agonistic antibodies (1 ng/ml) led to apoptosis of all rMF within 2 h, whereas activated HSC were more resistant (5.3 h/ 40% of total cells). Although transforming growth factor-β downregulated apoptosis in both activated HSC and rMF, tumor necrosis factor-α (TNF-α) upregulated apoptosis in rMF. Lack of spontaneous apoptosis and CD95L expression in rMF and the different reaction on TNF-α stimulation reveal that activated HSC and rMF belong to different cell populations. CD95 receptor CD95 ligand transforming growth factor-β Footnotes This study was supported by the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 402 Molekulare und Zelluläre Hepatogastroenterologie, project C6. Address for reprint requests and other correspondence: G. Ramadori, Dept. of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg August University Göttingen, Robert Koch Straße 40, 37075 Göttingen, Germany (E-mail: [email protected] ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. December 5, 2001;10.1152/ajpgi.00441.2001 Copyright © 2002 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver Physiology – The American Physiological Society

Published: Aug 1, 2002

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