Dataset Information

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

ABSTRACT:

Background and aim

Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset.

Methods

We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age- and sex-matched controls without inflammatory bowel disease (IBD).

Results

Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty-eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real-time reverse transcription polymerase chain reaction performed on ileal-derived RNA from 13 CD and nine non-IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort.

Conclusion

The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial- and virus-related genes in our CD-patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD.

SUBMITTER: Sim WH

PROVIDER: S-EPMC7167032 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

Sim Winnie H WH Wagner Josef J Cameron Donald J DJ Catto-Smith Anthony G AG Bishop Ruth F RF Kirkwood Carl D CD

Journal of gastroenterology and hepatology 20120601 6

<h4>Background and aim</h4>Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset.<h4>Methods</h4>We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age- and sex-matched controls without inflammatory bowel disease (IBD).<h4>Results</h4>Sequence analysis of 1000 ...[more]

PMID: 22098497

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Project description:BackgroundThe development and course of Crohn's disease (CD) is related to both genetic and environmental factors. Smoking has been found to exacerbate the course of CD by increasing the risk of developing fistulas and strictures as well as the need for surgery, possibly because of an interaction between smoking or nicotine on macrophage function and the intestinal microvasculature. Several genes are involved in the pathogenesis of CD, and in this study the gene expression differences of the descending colonic mucosa were investigated in CD (smokers or never smokers) and controls (smokers or never smokers).AimTo identify any difference in gene expression of the descending colonic mucosa between smoking and never-smoking CD patients (and controls) by determining genetic expression profiles from microarray analysis.MethodsFifty-seven specimens were obtained by routine colonoscopy from the included material: CD smokers (n = 28) or never-smokers (n = 14) as compared to fifteen healthy controls (8 smokers and 7 never-smokers). RNA was isolated and gene expression assessed with Affymetrix GeneChip Human Genome U133 Plus 2.0. Data were analyzed by principal component analysis (PCA), Wilcoxon rank sum test and multiple linear regressions. Real-time (RT) PCR was subsequently applied to verify microarray results.ResultsThe PCA analysis showed no intrinsic clustering of smokers versus never-smokers. However, when Wilcoxon rank sum test corrected with Q values were performed, six known genes were significantly expressed differently in the inflamed CD smokers as compared to the inflamed CD never-smokers: ring finger protein 138 (RNF138), metalothionein 2A (MT2A) and six transmembrane epithelial antigen of the prostate 3 (STEAP3), SA hypertension-associated homolog, PGM2L1 and KCNJ2. The subsequent RT-PCR-analyses verified, however, that only RNF138, MT2A and STEAP3 were significantly up-regulated in CD smokers in specimens with inflammatory activity of the descending colon.ConclusionsThe present study demonstrates that the genes, RNF138, MT2A, and STEAP3 are differently expressed in the inflamed descending colon of smoking versus never-smoking CD patients, which might be of relevance for the poorer clinical course among CD smokers. Many gastroenterologists are still not totally aware of the benefits of smoking cessation in relation to CD, and do not put much effort into getting the patients to quit, therefore more information on the negative effects of smoking, seems warranted.

Dataset Information

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

Background and aim

Methods

Results

Conclusion

Publications

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

Similar Datasets

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