Open AccessGenome‐wide expression profiling implicates a MAST3 ‐regulated gene set in colonic mucosal inflammation of ulcerative colitis patients
Author(s) -
Labbé Catherine,
Boucher Gabrielle,
Foisy Sylvain,
Alikashani Azadeh,
Nkwimi Herbert,
David Geneviève,
Beaudoin Mélissa,
Goyette Philippe,
Charron Guy,
Xavier Ramnik J.,
Rioux John D.
Publication year - 2012
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21887
Subject(s) - ulcerative colitis , gene expression , inflammatory bowel disease , biology , proinflammatory cytokine , gene expression profiling , immunology , immune system , inflammation , gene , gene knockdown , regulation of gene expression , colitis , genome wide association study , ccl20 , cancer research , chemokine , genetics , medicine , disease , pathology , single nucleotide polymorphism , genotype , chemokine receptor
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. (Inflamm Bowel Dis 2012)