title: Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays.
abstract: BACKGROUND
  The differential pathophysiologic mechanisms that trigger and maintain the two forms of inflammatory bowel disease (IBD), Crohn disease (CD), and ulcerative colitis (UC) are only partially understood. cDNA microarrays can be used to decipher gene regulation events at a genome-wide level and to identify novel unknown genes that might be involved in perpetuating inflammatory disease progression.
  
  
  RESULTS
  High-density cDNA microarrays representing 33,792 UniGene clusters were prepared. Biopsies were taken from the sigmoid colon of normal controls (n = 11), CD patients (n = 10) and UC patients (n = 10). 33P-radiolabeled cDNA from purified poly(A)+ RNA extracted from biopsies (unpooled) was hybridized to the arrays. We identified 500 and 272 transcripts differentially regulated in CD and UC, respectively. Interesting hits were independently verified by real-time PCR in a second sample of 100 individuals, and immunohistochemistry was used for exemplary localization. The main findings point to novel molecules important in abnormal immune regulation and the highly disturbed cell biology of colonic epithelial cells in IBD pathogenesis, e.g., CYLD (cylindromatosis, turban tumor syndrome) and CDH11 (cadherin 11, type 2). By the nature of the array setup, many of the genes identified were to our knowledge previously uncharacterized, and prediction of the putative function of a subsection of these genes indicate that some could be involved in early events in disease pathophysiology.
  
  
  CONCLUSIONS
  A comprehensive set of candidate genes not previously associated with IBD was revealed, which underlines the polygenic and complex nature of the disease. It points out substantial differences in pathophysiology between CD and UC. The multiple unknown genes identified may stimulate new research in the fields of barrier mechanisms and cell signalling in the context of IBD, and ultimately new therapeutic approaches.
authors.affiliation: Institute for Clinical Molecular Biology, University Hospital Schleswig Holstein, Christian-Albrechts University of Kiel, Kiel, Germany.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Costello
authors.forename: Nancy
authors.initials: N
authors.lastname: Mah
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Georg H
authors.initials: GH
authors.lastname: Waetzig
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.forename: Tim
authors.initials: T
authors.lastname: Lu
authors.forename: Yesim
authors.initials: Y
authors.lastname: Gurbuz
authors.forename: Susanna
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Mario
authors.initials: M
authors.lastname: Albrecht
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Ralph
authors.initials: R
authors.lastname: Lucius
authors.forename: Günther
authors.initials: G
authors.lastname: Klöppel
authors.forename: Holger
authors.initials: H
authors.lastname: Eickhoff
authors.forename: Hans
authors.initials: H
authors.lastname: Lehrach
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000378:metabolism; D000074749:Deubiquitinating Enzyme CYLD; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D064546:Protein Kinase C beta; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D025521:Tumor Suppressor Proteins; D011493:Protein Kinase C; D064546:Protein Kinase C beta; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD