title: Genome-wide expression profiling implicates a MAST3-regulated gene set in colonic mucosal inflammation of ulcerative colitis patients.
abstract: BACKGROUND
  Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) presumably caused by dysregulated immune responses to the gut microbiota. Genetic association studies have implicated dozens of chromosomal regions or loci in IBD susceptibility. The next challenge is to explain the individual role of each of these modest effect loci in the disease state. We have previously identified MAST3 as an IBD susceptibility gene through genetic fine-mapping of the 19p linkage region. Testing MAST3 in a reporter assay provided preliminary evidence that MAST3 modulates the activity of inflammation-related transcription factor nuclear factor kappa B.
  
  
  METHODS
  Here we characterized the function of MAST3 through an examination of the influence of the modulation of MAST3 expression on endogenous genome-wide expression patterns. More specifically, we looked at differential gene expression resulting from overexpression and knockdown of the MAST3 gene in epithelial and macrophage cell lines. From we highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-jB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD.
  
  
  RESULTS
  We highlight a group of genes whose expression is modulated by MAST3 and correlate their expression with NF-κB activity. Their expression was found to be enriched in inflamed mucosal tissue of UC patients, confirming the importance of these genes in IBD. These MAST3-regulated genes are central to mucosal immune responses. Among them are proinflammatory cytokines (e.g., CCL20, IL8), regulators of NF-κB (e.g., TNFAIP3, LY96, NFKBIA), genes involved in interferon-induced defense against pathogen invasion (e.g., IFIT1, ISG15), and genes involved in cell adhesion and/or migration (e.g., CD44, TMOD1).
  
  
  CONCLUSIONS
  Taken together, these results confirm MAST3 as a modulator of the inflammatory response through regulation of immune gene expression in the gut of IBD patients.
authors: Institut de Cardiologie de Montréal, Montréal, Quebec, Canada.
authors: Catherine
authors: C
authors: Labbé
authors: Gabrielle
authors: G
authors: Boucher
authors: Sylvain
authors: S
authors: Foisy
authors: Azadeh
authors: A
authors: Alikashani
authors: Herbert
authors: H
authors: Nkwimi
authors: Geneviève
authors: G
authors: David
authors: Mélissa
authors: M
authors: Beaudoin
authors: Philippe
authors: P
authors: Goyette
authors: Guy
authors: G
authors: Charron
authors: Ramnik J
authors: RJ
authors: Xavier
authors: John D
authors: JD
authors: Rioux
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D052016:Mucositis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C544700:MAST3 protein, human; D017346:Protein Serine-Threonine Kinases