The bcl, NFκB and p53/p21WAF1 systems are involved in spontaneous apoptosis and in the anti-apoptotic effect of TGF-β or TNF-α on activated hepatic stellate cells
| Autor: | Hammoudeh El Armouche, Katrin Neubauer, Nina Matthes, Giuliano Ramadori, Bernhard Saile |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Histology Down-Regulation Apoptosis Transfection Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Bcl-2-associated X protein Transforming Growth Factor beta Cyclins Proto-Oncogene Proteins Gene expression Animals Rats Wistar Cells Cultured bcl-2-Associated X Protein 030304 developmental biology Regulation of gene expression 0303 health sciences biology Tumor Necrosis Factor-alpha NF-kappa B Cell Biology General Medicine Genes p53 Fas receptor Genes bcl-2 Rats Up-Regulation 3. Good health Cell biology Gene Expression Regulation Liver Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis biology.protein Cancer research Hepatic stellate cell Transforming growth factor |
| Zdroj: | European Journal of Cell Biology. 80:554-561 |
| ISSN: | 0171-9335 |
| Popis: | Activated hepatic stellate cells (HSC) are thought to play a pivotal role in development of liver fibrosis which takes place in chronic liver diseases. Previous studies have shown that "activated" rat HSC undergo spontaneous apoptosis probably through the CD95/CD95L pathway. TGF-beta as well as TNF-alpha reduced spontaneous apoptosis and CD95L expression. The aim of this study was to investigate the possible mechanisms responsible for the spontaneous apoptosis and for the anti-apoptotic effect of TGF-beta and TNF-alpha on activated HSC. While bcl-2, bax, NFkappaB and p53 gene expression were spontaneously upregulated, bcl-xL and p21WAF1 gene expression decreased and IkappaB remained unchanged during the activation process in vitro. TGF-beta as well as TNF-alpha induced activation of NFKB and upregulated bcl-xL. The latter was inhibited by overexpression of IkappaB. By suppressing spontaneous apoptosis TGF-beta as well as TNF-alpha inhibited p53 gene expression while that of the p21WAF1 gene was increased. We conclude that TGF-beta as well as TNF-alpha may act as surviving factors for activated rat HSC not only through reduction of CD95L gene expression but also by upregulating the anti-apoptotic factors NFKB, bcl-xL and p21WAF1 and by downregulating the proapoptotic factor p53. The interaction with these factors may lead to the generation of new antifibrotic drugs. |
| Databáze: | OpenAIRE |
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