MORT1/FADD is involved in liver regeneration.
OBJECTIVE
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.


CONCLUSIONS
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.
Schuchmann
Marcus
M
Department of Medicine University of Mainz, Langenbeckstr. 1, Mainz 55101, Germany. schuchm@mail.uni-mainz.de
Ruckert
Felix
F
Garcia-Lazaro
Jose F
JF
Karg
Andrea
A
Burg
Jurgen
J
Knorr
Natalia
N
Siebler
Jurgen
J
Varfolomeev
Eugene E
EE
Wallach
David
D
Schreiber
Wolfgang
W
Lohse
Ansgar W
AW
Galle
Peter R
PR
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D019925:Cyclin A / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D006498:Hepatectomy; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D019925:Cyclin A; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D015850:Interleukin-6; D010446:Peptide Fragments