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

Authors
  • Sim, Winnie H1
  • Wagner, Josef
  • Cameron, Donald J
  • Catto-Smith, Anthony G
  • Bishop, Ruth F
  • Kirkwood, Carl D
  • 1 Enteric Virus Group, Murdoch Children's Research Institute, Victoria, Australia. [email protected] , (Australia)
Type
Published Article
Journal
Journal of Gastroenterology and Hepatology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2012
Volume
27
Issue
6
Pages
1083–1093
Identifiers
DOI: 10.1111/j.1440-1746.2011.06973.x
PMID: 22098497
Source
Medline
Language
English
License
Unknown

Abstract

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. 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). 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. 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. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

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