Fas engagement accelerates liver regeneration after partial hepatectomy

Abstract

Fas (CD95) is a receptor involved in induction of apoptotic cell death of Fas-bearing cells, including hepatocytes1,2 and T cells3. Injection of Fas-specific antibodies into mice leads to fulminant hepatic failure and death1. Fas also transduces growth-promoting signals in proliferating T cells4,5, fibroblasts6 and some tumor cells7. Here we show that partial hepatectomy, which triggers the immediate onset of liver regeneration8, protected mice against the lethal effects of Fas-specific antibodies and prevented hepatocyte apoptosis in response to Fas engagement in vivo. Furthermore, Fas engagement accelerated liver regeneration after partial hepatectomy. Liver regeneration kinetics were delayed in mutant mice with decreased cell surface Fas expression (lpr mice9). In contrast, regeneration was not delayed in lpr-cg mutant mice, which have a Fas mutation that prevents Fas-induced death10 but not Fas-dependent proliferative stimulation. Our results indicate that Fas engagement on cells in regenerating or healing tissues may promote cell growth.

Cite this article

Desbarats, J., Newell, M. Fas engagement accelerates liver regeneration after partial hepatectomy. Nat Med 6, 920–923 (2000). https://doi.org/10.1038/78688

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