Vol. 283, Issue 2, G435-G444, August 2002
Rat liver myofibroblasts and hepatic stellate cells differ in
CD95-mediated apoptosis and response to TNF-
Bernhard
Saile,
Nina
Matthes,
Katrin
Neubauer,
Christoph
Eisenbach,
Hammoudeh
El-Armouche,
Joszef
Dudas, and
Giuliano
Ramadori
Department of Internal Medicine, Section of
Gastroenterology and Endocrinology, University of Göttingen,
37075 Göttingen, Germany
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-
downregulated
apoptosis in both activated HSC and rMF, tumor necrosis
factor-
(TNF-) upregulated apoptosis in rMF. Lack of
spontaneous apoptosis and CD95L expression in rMF and the
different reaction on TNF- stimulation reveal that activated HSC and
rMF belong to different cell populations.
CD95 receptor; CD95 ligand; transforming growth factor-
