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| Status |
Public on Sep 03, 2014 |
| Title |
TNFR1 controls apoptosis and chronic liver disease in hepatocyte-specific IKKγ (Nemo) mice. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Death receptor-mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion injury, fulminant hepatic failure, cholestatic liver injury and cancer. Deletion of NF-ĸB essential modulator in hepatocytes (NemoΔhepa) causes the spontaneous development of hepatocellular carcinoma preceded by steatohepatitis in mice and thus serves as an excellent model for the progression from chronic hepatitis to liver cancer. In the present study we aimed to dissect the death-receptor mediated pathways that contribute to liver injury in NemoΔhepa mice. Therefore, we generated NemoΔhepa/TRAIL-/- and NemoΔhepa/TNFR1-/- animals and analyzed the progression of liver injury. NemoΔhepa/TRAIL-/- displayed a similar phenotype to NemoΔhepa mice characteristic of high apoptosis, infiltration of immune cells, hepatocyte proliferation and steatohepatitis. These pathophysiological features were significantly ameliorated in NemoΔhepa/TNFR1-/- livers. Hepatocyte apoptosis was increased in NemoΔhepa and NemoΔhepa/TRAIL-/- mice while NemoΔhepa/TNFR1-/- animals showed reduced cell death concomitant with a strong reduction in pJNK levels. Cell cycle parameters were significantly less activated in NemoΔhepa/TNFR1-/- livers. Additionally, markers of liver fibrosis and indicators of tumour progression were significantly decreased in these animals. The present data demonstrate that the death receptor TNFR1 but not TRAIL is important in determining progression of liver injury in hepatocyte-specific Nemo knockout mice.
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| Overall design |
Expression profiling of livers from wild type, NEMO, NEMO-TRIAL, and NEMO-TNFR null mice
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| Contributor(s) |
Singh A, Cubero FJ, Borkham-Kamphorst E, Nevzorova YA, Al Masaoudi M, Boekschoten MV, Gassler N, Weiskirchen R, Luedde T, Heikenwalder M, Müller M, Liedtke C, Trautwein C |
| Citation(s) |
23933814 |
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| Submission date |
Oct 23, 2011 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA149175 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33161_RAW.tar |
44.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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