Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.

E-GEOD-21266 - Effect of Ursodeoxycholic acid on gene expression in the intestial epithelium

Status
Released on 1 July 2011, last updated on 12 July 2011
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (8)
Description
Background & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy. Six normal mice were used for isolation of control RNA and six mice were used for isolation of RNA after UDCA treatment. RNAs of two animals were pooled i.e. there were six treated samples, named T1+2;T3+4,T5+6 and six nontreated samples named N1+2;N3+4 and N5+6.
Experiment type
transcription profiling by array 
Contacts
christoph Hanski <christoph.hanski@charite.de>, Christoph Hanski, Santosh Krishna-Subramanian
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-21266.idf.txt
Sample and data relationshipE-GEOD-21266.sdrf.txt
Raw data (1)E-GEOD-21266.raw.1.zip
Processed data (1)E-GEOD-21266.processed.1.zip
Array designA-AFFY-36.adf.txt
R ExpressionSetE-GEOD-21266.eSet.r
Links