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

2002, American Journal of Physiology-gastrointestinal and Liver Physiology

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 Ϯ 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.

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