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Series GSE30651 Query DataSets for GSE30651
Status Public on Jul 11, 2012
Title Conditional elimination of c-Met signaling in the liver aggravates oxidative stress and cholestasis, and deregulates lipid metabolism, under a high cholesterol diet
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background: Genetic elimination of c-Met signaling in the liver has been shown to impact many cellular pathways involved in repair, regeneration, lipid homeostasis and redox balance. In this study, we analyzed a nutritional model of hepatic steatosis in Met fl/fl ; Alb-Cre +/- (MetKO) mice in a 129SV/C57BL/6 background fed a high cholesterol diet for 30 days.

Methods: Liver injury was determined by histopathology and plasma enzymes, transcriptomic changes were examined using gene expression microarrays, and evaluation of key molecules involved in liver damage and lipid homestasis were evaluated by Western blot analysis.

Results: We observed that in comparison with wild type mice subjected to the same diet, MetKO mice developed a strong liver lipid deposition, inflammatory infiltration and increment in total bile acids synthesis and liver damage markers. Global transcriptomic changes analysis confirmed the steatosis and cholestasis induced by the high cholesterol diet. In addition, we found affected pathways related to amino acids, glutathione and lipid metabolism, oxidative stress and mitochondria dysfunction. Oxidative stress exacerbation was corroborated by lipid and protein oxidation in liver tissue. To address further, Western blot studies revealed downregulation on Erk, NF-kB and Nrf2 survival pathways and target genes (cyclin D1, SOD1, gamma-GCS), an increment in proapoptotic proteins (p53, caspase 3) and changes in nuclear receptors such as RAR and RXR, which were increased, and CAR, FXR and PPAR alfa, which were decreased, in the MetKO diet. These results are in agreement with the steatosis and cholestasis phenotype.

Conclusion: Our data provide evidence of c-Met signaling involvement in lipid metabolism, and bile acids synthesis and excretion. Disruption of these pathways leads to liver dysfunction, improper metabolism and hepatocellular damage.
 
Overall design Global transcriptome changes between WT mice vs. c-Met KO mice fed a 2% cholesterol and 0.5% sodium cholate diet (high cholesterol) or a Chow regular diet (Chow) as control. Mice were fed a high cholesterol or chow regular diet for 30 days. Liver tissue was obtained, and RNA was extracted and subjected to Illumina microarray analysis.
 
Contributor(s) Gomez-Quiroz LE, Seo D, Gillen M, Thorgeirsson SS
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Submission date Jul 13, 2011
Last update date Jun 14, 2018
Contact name Daekwan Seo
E-mail(s) daekwan_seo@nih.gov
Phone 301-496-5688
Fax 301-496-0734
Organization name NIH
Department NCI
Lab LEC
Street address 37 Convent Dr. Rm 4140
City Bethesda
State/province MD
ZIP/Postal code 20878
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (16)
GSM759949 Chow Diet, WT mice, rep1
GSM759950 Chow Diet, WT mice, rep2
GSM759951 Chow Diet, WT mice, rep3
Relations
BioProject PRJNA144613

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
GSE30651_RAW.tar 3.1 Mb (http)(custom) TAR
GSE30651_non-normalized.txt.gz 2.8 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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