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Series GSE8969 Query DataSets for GSE8969
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
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
 
Overall design Livers from Nrf2 k.o. and wt mice; 3 hybridizations per genoype: RNA samples were pooled from 3 individual animals
 
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
Organization name ETH Zurich
Department Genetic Diversity Centre
Street address Universitatstrasse 16
City Zurich
ZIP/Postal code 8092
Country Switzerland
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
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
Relations
BioProject PRJNA102419

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE8969_RAW.tar 22.0 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data included within Sample table

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