Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2005; 11(46): 7248-7253
Published online Dec 14, 2005. doi: 10.3748/wjg.v11.i46.7248
MORT1/FADD is involved in liver regeneration
Marcus Schuchmann, Felix Rückert, Jose F Garcia-Lazaro, Andrea Karg, Jürgen Burg, Natalia Knorr, Jürgen Siebler, Eugene E Varfolomeev, David Wallach, Wolfgang Schreiber, Ansgar W Lohse, Peter R Galle
Marcus Schuchmann, Felix Rückert, Jose F Garcia-Lazaro, Natalia Knorr, Jürgen Siebler, Ansgar W Lohse, Peter R Galle, I. Department of Medicine, University of Mainz, Langenbeckstr. 1, Mainz 55101, Germany
Andrea Karg, Wolfgang Schreiber, Institute of Radiology, University of Mainz, Langenbeckstr. 1, Mainz 55101, Germany
Jürgen Burg, Institute of Pathology, University of Mainz, Langenbeckstr. 1, Mainz 55101, Germany
Eugene E Varfolomeev, Genentech, South San Francisco, CA, United States
David Wallach, The Weizmann Institute of Science, Rehovot, Israel
Author contributions: All authors contributed equally to the work.
Supported by the Intramural grant (MAIFOR) to M.S.
Correspondence to: Marcus Schuchmann, MD, I. Department of Medicine University of Mainz, Langenbeckstr. 1, Mainz 55101, Germany. schuchm@mail.uni-mainz.de
Telephone: +49-6131170 Fax: + 49-6131176-621
Received: March 18, 2005
Revised: June 23, 2005
Accepted: July 1, 2005
Published online: December 14, 2005
Abstract

AIM: To explore the role of the adaptor molecule in liver regeneration after partial hepatectomy (PH).

METHODS: We used transgenic mice expressing an N-terminal truncated form of MORT1/FADD under the control of the albumin promoter. As previously shown, this transgenic protein abrogated CD95- and CD120a-mediated apoptosis in the liver. Cyclin A expression was detected using Western blotting. ELISA and RT-PCR were used to detect IL-6 and IL-6 mRNA, respectively. DNA synthesis in liver tissue was measured by BrdU staining.

RESULTS: Resection of 70% of the liver was followed by a reduced early regenerative response in the transgenic group at 36 h. Accordingly, 36 h after hepatectomy, cyclin A expression was only detectable in wild-type animals. Consequently, the onset of liver mass restoration was retarded as measured by MRI volumetry and mortality was significantly higher in the transgenic group.

CONCLUSION: Our data demonstrate for the first time an involvement of the death receptor molecule MORT1/FADD in liver regeneration, beyond its well described role as part of the intracellular death signaling pathway.

Keywords: MORT1/FADD, CD95, TNF, Apoptosis, Liver regeneration