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Fas engagement accelerates liver regeneration after partial hepatectomy

Nature Medicine volume 6, pages 920–923 (2000)Cite this article

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.

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Figure 1: Partial hepatectomy prevents Fas-induced hepatocyte apoptosis and stimulates hepatocyte proliferation.
Figure 2: Liver regeneration is delayed in mice with decreased Fas expression.

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Acknowledgements

We thank S. Huber for animal care; S. Mischler and P.W. Nevin for advice on surgical technique; J. Kupperman, J. Rogers and J.E. Stone for technical assistance; C. Charland for flow cytometry assistance; J.Q. Russell, M.W. Roe and S. Lidofsky for advice on hepatocyte preparations; D. Davis for assistance with histology; and R.J. Melamede and S. Lidofsky for reviewing the manuscript. This research was supported by grant number 1RO1GM62562 from the National Institutes of Health, a postdoctoral fellowship from the Medical Research Council of Canada (J.D.), research support from the University of Vermont, and sponsored research from Immune Response Corporation, Carlsbad, California.

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  1. Department of Medicine, University of Vermont, Burlington, 05401, Vermont, USA

    Julie Desbarats & M. Karen Newell

  2. Department of Biology, 233 Science Building, University of Colorado at Colorado Springs, Colorado Springs, 80918, Colorado, USA

    Julie Desbarats & M. Karen Newell

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Correspondence to M. Karen Newell.

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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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