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Status |
Public on May 12, 2010 |
Title |
Microarray analysis of colonic mucosa gene expression in wild type and foxo4 knock out mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Analysis of mechano-regulation of tenocyte metabolism at gene expression level. The hypothesis tested in the present study was that cyclic tensile strain influence the balance of anabolism/catabolism of tenocytes.
Forkhead box O (FoxO) proteins are a family of transcription factors implicated in many biological processes including immune regulation. In this study, we found that mice null for Foxo4, a member of the FoxO family, are more susceptible to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis than wild type controls. To understand the mechanism of elevated colitis susceptibility and the nature of the TNBS-induced colitis in Foxo4-null mice, we performed microarray analysis with mucosal cDNA samples from large intestines of untreated, ethanol and TNBS-treated wild type and Foxo4 KO mice. Unexpectedly, we found that cytokine CCL5, CXCL9, TNFalpha, and IFNgamma were already significantly upregulated in untreated Foxo4-null mice compared to WT controls despite lack of visible colonic phenotypes. Consistent with the exacerbated inflammatory phenotype in TNBS-treated Foxo4 KO mice, expressions of these inflammatory cytokines are further upregulated after TNBS-treatment. In addition, we observed many more inflammatory cytokines that were upregulated in TNBS-treated Foxo4 KO mice, including chemokines (CCL3, 4, 7, 8, 11, 12, 21b and CXCL1, 12, 14), chemokine receptors (CCR7, CCRl2, 8,CXC3CR1), cytokines (IL-1, IL-6, IL-11, IFI205), and cytokine receptors (TNFrsf). Interestingly, many of the anti-bacterial peptides were also up-regulated in TNBS treated Foxo4 KO mice including defensin related cryptdin (Defcr3,5,6, 9,13) and Defcr related sequence (Defcr-cr1,2,10,12). Up-regulation of basal level of IFNgamma, TNFalpha, CCL5, and CXCL9 expression in Foxo4 KO mice is specific to colonic tissues, as no significant difference of these gene transcript levels between wild type and Foxo4 KO mice was observed in other tissues including thymus. IFNgamma, TNFalpha, and IL-1beta, which are upregulated in TNBS-treated Foxo4 KO mice, are Th1 type cytokines. This is consistent with the Th1 inflammatory phenotype observed in TNBS-treated Foxo4-KO mice. We also tested whether the expression of Th2 cytokines (IL-4, IL-5, and IL-13) is altered in TNBS-treated WT and Foxo4-null mice in comparison to ethanol-treated mice and observed no significant differences suggesting that the TNBS-induced colitis in Foxo4-null FVB mice is predominantly Th1 in nature.
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Overall design |
Colonic mucosal tissues from five mice per treatment group (untreated, two days after ethanol or TNBS-treatment) were pooled. Total RNA obtained from colon mucosa isolated tendon fascicles subjected to 1 or 24 hours in vitro cyclic tensile strain compared to unstrained control fascicles.
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Contributor(s) |
Zhou W, Liu Z |
Citation(s) |
19560465 |
Submission date |
May 08, 2009 |
Last update date |
Jan 18, 2013 |
Contact name |
wen zhou |
E-mail(s) |
wen.zhou@utsouthwestern.edu
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Phone |
214-648-4024
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Organization name |
UT Southwestern Medical Center at Dallas
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Department |
Internal Medicine ,Cardiology
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Lab |
Liu Lab
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Street address |
6000 Harry Hines Blvd NB11.110
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City |
Dallas |
State/province |
TX |
ZIP/Postal code |
75235 |
Country |
USA |
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Platforms (1) |
GPL6105 |
Illumina mouse-6 v1.1 expression beadchip |
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Samples (6)
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GSM401300 |
wild type mice two days after treatment of 250mg Trinitrobenzene Sulfonic Acid in 50% ethanol enema |
GSM401301 |
wild type mice two days after treatment of 50% ethanol enema |
GSM401302 |
foxo4 knock out mice two days after treatment of 250mg Trinitrobenzene Sulfonic Acid in 50% ethanol enema |
GSM401303 |
foxo4 knock out mice two days after treatment of 50% ethanol enema |
GSM401304 |
foxo4 knock out mice without treatment |
GSM401305 |
wild type mice without treatment |
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Relations |
BioProject |
PRJNA115391 |
Supplementary file |
Size |
Download |
File type/resource |
GSE16033_RAW.tar |
5.2 Mb |
(http)(custom) |
TAR |
GSE16033_matrix_unnormalized.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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