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| Status |
Public on Jan 15, 2008 |
| Title |
Impaired liver regeneration in Nrf2 knockout mice caused by ROS-mediated insulin/IGF-1 resistance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The liver is frequently challenged by surgery-induced metabolic overload, viruses, or toxins, which induce the formation of reactive oxygen species. To determine the effect of oxidative stress on liver regeneration and to identify the underlying signalling pathways, we studied liver repair in mice lacking the Nrf2 transcription factor. In these animals, expression of several cytoprotective enzymes was reduced in hepatocytes, resulting in oxidative stress. As a consequence, tissue damage was aggravated, and liver regeneration after partial hepatectomy was delayed.
Using in vitro and in vivo studies we identified oxidative stress-induced insulin/insulin-like growth factor resistance as the underlying mechanism. This deficiency impaired the activation of p38 mitogen-activated kinase, Akt kinase, and downstream targets after hepatectomy, resulting in enhanced death and delayed proliferation of hepatocytes. Our results reveal novel roles of Nrf2 in the regulation of growth factor signalling and in tissue repair. In addition, they provide new insight into the mechanisms underlying oxidative stress-induced defects in liver regeneration and thus offer new avenues to improve regeneration in patients with acute or chronic liver damage.
Keywords: genetic modification, wilde type (wt) vs. knock out (k.o.) liver samples
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| Overall design |
Livers from Nrf2 k.o. and wt mice; 3 hybridizations per genoype: RNA samples were pooled from 3 individual animals
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| Contributor(s) |
Beyer TA, Werner S |
| Citation(s) |
18059474 |
| Submission date |
Sep 06, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Stefan Zoller |
| E-mail(s) |
szoller@env.ethz.ch
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| Organization name |
ETH Zurich
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| Department |
Genetic Diversity Centre
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| Street address |
Universitatstrasse 16
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| City |
Zurich |
| ZIP/Postal code |
8092 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| GSM227407 |
Liver from Nrf2 k.o. mice, biological replicate 1 |
| GSM227408 |
Liver from Nrf2 k.o. mice, biological replicate 2 |
| GSM227409 |
Liver from Nrf2 k.o. mice, biological replicate 3 |
| GSM227410 |
Liver from Nrf2 wt mice, biological replicate 1 |
| GSM227411 |
Liver from Nrf2 wt mice, biological replicate 2 |
| GSM227412 |
Liver from Nrf2 wt mice, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA102419 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8969_RAW.tar |
22.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
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