E-GEOD-8969 - Transcription profiling of mouse Nrf2 knockout caused by ROS-mediated insulin/IGF-1 resistance

Status
Submitted on 6 September 2007, released on 16 June 2008, last updated on 2 May 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (5)
Description
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. Experiment Overall Design: Livers from Nrf2 k.o. and wt mice; 3 hybridizations per genoype: RNA samples were pooled from 3 individual animals
Experiment types
transcription profiling by array, unknown experiment type
Contact
Citation
Impaired liver regeneration in Nrf2 knockout mice: role of ROS-mediated insulin/IGF-1 resistance. Tobias A Beyer, Weihua Xu, Daniel Teupser, Ulrich auf dem Keller, Philippe Bugnon, Eberhard Hildt, Joachim Thiery, Yuet Wai Kan, Sabine Werner. EMBO J 27(1):212-23 (2008)
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-8969.idf.txt
Sample and data relationshipE-GEOD-8969.sdrf.txt
Raw data (1)E-GEOD-8969.raw.1.zip
Processed data (1)E-GEOD-8969.processed.1.zip
Array designA-AFFY-45.adf.txt
R ExpressionSetE-GEOD-8969.eSet.r
Links