RGD Reference Report - CD95 ligand is a proliferative and antiapoptotic signal in quiescent hepatic stellate cells. - Rat Genome Database

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CD95 ligand is a proliferative and antiapoptotic signal in quiescent hepatic stellate cells.

Authors: Reinehr, R  Sommerfeld, A  Haussinger, D 
Citation: Reinehr R, etal., Gastroenterology. 2008 May;134(5):1494-506. Epub 2008 Feb 14.
RGD ID: 2315731
Pubmed: PMID:18471522   (View Abstract at PubMed)
DOI: DOI:10.1053/j.gastro.2008.02.021   (Journal Full-text)

BACKGROUND & AIMS: Despite expression of CD95 (Fas) receptor, hepatic stellate cells (HSCs) are fairly resistant toward CD95 ligand (CD95L)-induced cell death. The underlying mechanisms and the function of the CD95 system in quiescent HSCs, however, are unknown. METHODS: The effects of CD95L on quiescent, 1- to 2-day cultured rat HSCs were studied with regard to CD95 activation, signal transduction, proliferation, and apoptosis. RESULTS: In quiescent HSCs, CD95L led to a rapid phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (Erk), and c-Src, but not of c-Jun-N-terminal kinase and p47(phox), an activating subunit of reduced nicotinamide adenine dinucleotide phosphate oxidase. CD95L-induced EGFR and Erk phosphorylation were abolished after proteinase inhibition by GM6001 and in the presence of neutralizing epidermal growth factor antibodies, suggestive of a ligand-dependent EGFR phosphorylation in response to CD95L. In quiescent HSCs, CD95L did not induce apoptotic cell death but stimulated HSC proliferation and triggered a rapid inactivating CD95 tyrosine nitration that was not detected in activated HSCs (10-14 days of culture). EGFR phosphorylation, HSC proliferation, and CD95 tyrosine nitration were also triggered by tumor necrosis factor alpha and tumor necrosis factor-related apoptosis-inducing ligand. CONCLUSIONS: In quiescent HSCs, CD95L and other death receptor ligands are mitogens through a ligand-dependent EGFR phosphorylation. Simultaneously, an antiapoptotic signaling is triggered by CD95L-induced CD95 tyrosine nitration. This unusual response to death receptor ligands may help quiescent HSCs to participate in liver regeneration following liver injury.

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Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Faslg  (Fas ligand)


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