Fas engagement accelerates liver regeneration after partial hepatectomy.
Fas (CD95) is a receptor involved in induction of apoptotic cell death of Fas-bearing cells, including hepatocytes and T cells. Injection of Fas-specific antibodies into mice leads to fulminant hepatic failure and death. Fas also transduces growth-promoting signals in proliferating T cells, fibroblasts and some tumor cells. Here we show that partial hepatectomy, which triggers the immediate onset of liver regeneration, 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 mice). In contrast, regeneration was not delayed in lpr-cg mutant mice, which have a Fas mutation that prevents Fas-induced death but not Fas-dependent proliferative stimulation. Our results indicate that Fas engagement on cells in regenerating or healing tissues may promote cell growth.
Department of Medicine, University of Vermont, Burlington, Vermont 05401, USA.
J
J
Desbarats
M K
MK
Newell
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D017209:Apoptosis / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D005260:Female; D006498:Hepatectomy; D008099:Liver / Q000166:cytology / Q000276:immunology; D008115:Liver Regeneration / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D019014:fas Receptor