title: Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Enteric Virus Group, Murdoch Children's Research Institute, Victoria, Australia. winnie.h.sim@gmail.com
authors.forename: Winnie H
authors.initials: WH
authors.lastname: Sim
authors.forename: Josef
authors.initials: J
authors.lastname: Wagner
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Cameron
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Catto-Smith
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Bishop
authors.forename: Carl D
authors.initials: CD
authors.lastname: Kirkwood
mesh_terms: D000293:Adolescent; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D051847:Lithostathine / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015854:Up-Regulation
chemical_list: D051847:Lithostathine; C497617:REG1A protein, human; D020778:Matrix Metalloproteinase 2
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