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| Status |
Public on Sep 01, 2010 |
| Title |
Gene expression study identifies important protective pathways utilized by appendicitis and appendectomy for ameliorating colitis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
BACKGROUND: Appendicitis followed by appendectomy (AA) at a young age protects against later inflammatory bowel disease (IBD). Using a novel murine appendicitis model we earlier demonstrated that AA proffered significant protection against subsequent experimental colitis.
AIM: To delineate genes and biological pathways involved in the protective effect of AA against subsequent colitis using gene set enrichment analysis (GSEA) of DNA microarray data.
METHODS: Appendicitis and appendicectomy was done (5 week old male BALB/c mice) near the most proximal colon (caecal lymphoid follicles) and colonic samples were harvested from the most distal colon. Two consecutive laparotomies were done in control Sham-Sham (SS) mice. RNA was extracted (TRIzol®) from 4 individual colonic samples per group (AA group vs. SS group) with each sample taken independently through Affymetrix® microarray hybridization. For GSEA, data for more than 23,000 genes were exported from Partek and analyzed with GSEA software (with 2852 gene sets encoded) to establish correlates with phenotypes of the gene sets.
RESULTS: Distal colonic expression of 636 gene-sets were significantly upregulated in AA group samples (False Discovery Rates (FDR) values < 1 % and p value < 0.001; stringent statistical selection). These were validated by quantitative PCR of 14 selected genes across the immunological spectrum and over time-intervals of 3 days, 14 days and 28 days.
CONCLUSIONS: Many key immunological, apoptosis-related and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. Further analysis of these profiles and biological pathways will assist utilizing these gene products and manipulating various aspects of these pathways to develop better therapeutic strategies in the management of intractable IBD.
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| Overall design |
Appendicitis and appendicectomy was done (5 week old male BALB/c mice) near the most proximal colon (caecal lymphoid follicles) and colonic samples were harvested from the most distal colon. Two consecutive laparotomies were done in control Sham-Sham (SS) mice. RNA was extracted (TRIzol®) from 4 individual colonic samples per group (AA group vs. SS group) with each sample taken independently through Affymetrix® microarray hybridization.
variable_protocol: appendicitis and appendectomy: AA1, AA2, AA3, AA4
variable_protocol: sham/sham surgery: SS1, SS2, SS3, SS4
repeat_biological replicate: AA1, AA2, AA3, AA4
repeat_biological replicate: SS1, SS2, SS3, SS4
Upregulated gene-set linked as supplementary file.
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| Contributor(s) |
Cheluvappa R, Luo AS, Palmer C, Kaplan W, Cowley MJ, Grimm MC |
| Citation(s) |
21707591, 25085204, 30037025, 24666024 |
| Submission date |
Sep 01, 2010 |
| Last update date |
Sep 11, 2019 |
| Contact name |
Rajkumar Cheluvappa |
| E-mail(s) |
rajkumarchel@gmail.com
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| Phone |
+61 0406 0406 20
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| Organization name |
University of New South Wales
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| Department |
St George Clinical School
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| Lab |
Inflammation and nfection Research Centre
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| Street address |
Inflammation and Infection Research Centre, School of Medical Sciences, Wallace Wurth Building, University of New South Wales, Gate 9 High Street, Sydney, NSW 2052, Australia.
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| City |
Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2052 |
| Country |
Australia |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| GSM589700 |
Appendicitis induction followed by appendicectomy after 1 week No. 1 |
| GSM589701 |
Appendicitis induction followed by appendicectomy after 1 week No. 2 |
| GSM589702 |
Appendicitis induction followed by appendicectomy after 1 week No. 3 |
| GSM589703 |
Appendicitis induction followed by appendicectomy after 1 week No. 4 |
| GSM589704 |
1st Sham surgery followed by 2nd sham surgery after 1 week No. 1 |
| GSM589705 |
1st Sham surgery followed by 2nd sham surgery after 1 week No. 2 |
| GSM589706 |
1st Sham surgery followed by 2nd sham surgery after 1 week No. 3 |
| GSM589707 |
1st Sham surgery followed by 2nd sham surgery after 1 week No. 4 |
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| Relations |
| BioProject |
PRJNA130527 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23914_Appendicitis_and_3_days_PostAppendectomy_UP.txt.gz |
4.7 Kb |
(ftp)(http) |
TXT |
| GSE23914_RAW.tar |
33.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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