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Am J Physiol Gastrointest Liver Physiol (December 5, 2001). doi:10.1152/ajpgi.00441.2001
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Articles in PresS, published online ahead of print December 5, 2001
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00441.2001
Submitted on October 15, 2001
Accepted on November 26, 2001

Rat Liver Myofibroblasts and Hepatic Stellate Cells differ in CD95-mediated Apoptosis and in their Response to TNF-{alpha}

Bernhard Saile1, Nina Matthes1, Katrin Neubauer1, Christoph Eisenbach1, Hammoudeh El-Armouche1, Joszef Dudas1, and Giuliano Ramadori1*

1 Gastroenterology and Endocrinology, University of Goettingen, Goettingen, Germany

* To whom correspondence should be addressed. E-mail: bsaile{at}gwdg.de.

Hepatic stellate cells (HSC) in particular 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 liver myofibroblasts (rMF) also have fibrogenic potential. A major difference between the two cell types is the different life span under culture conditions. While nearly no spontaneous apoptosis could be shown in rMF- cultures, 18%±2% of the activated HSC (d7) were apoptotic. Compared to 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 (1ng/ml) led to apoptosis of all rMF within 2h whereas activated HSC were more resistant (5.3h/ 40% of total cells). While TGF-ß downregulated apoptosis in both activated HSC and rMF, TNF-{alpha} upregulated apoptosis in rMF. The lack of spontaneous apoptosis and CD95L expression in rMF as well as the different reaction upon TNF-{alpha} stimulation reveal that activated HSC and rMF belong to different cell populations.






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