TY - JOUR
T1 - MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α
AU - Wu, Feng
AU - Zikusoka, Michelle
AU - Trindade, Anil
AU - Dassopoulos, Themistocles
AU - Harris, Mary L.
AU - Bayless, Theodore M.
AU - Brant, Steven R.
AU - Chakravarti, Shukti
AU - Kwon, John H.
N1 - Funding Information:
Supported by National Institutes of Health grants K08DK078046 (to J.H.K.) and R24DK064388 and by Broad Medical Research Program grants IBD-0051 (to F.W. and S.C.) and IBD-0212 (F.W. and J.H.K.). J.H.K. was also supported by the Sherlock Hibbs IBD Research Fund, the M. Alan Guerrieri Family Fund and the Meyerhoff IBD Center at The Johns Hopkins University.
PY - 2008/11
Y1 - 2008/11
N2 - Background & Aims: Chronic inflammatory bowel diseases such as ulcerative colitis (UC) are associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNAs (miRNAs), which direct mRNA degradation and translational inhibition, influence a number of disease processes. We examined whether miRNAs are differentially expressed in UC tissues and are associated with expression of genes that regulate inflammation. Methods: miRNA expression was assessed in patients with active UC, inactive UC, Crohn's disease, irritable bowel syndrome, infectious colitis, and microscopic colitis, as well as in healthy subjects by microarray, quantitative reverse transcription-polymerase chain reaction and in situ hybridization analyses. Colonic epithelial cell (HT29) expression of miRNAs was assessed. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics. Results: Active UC was associated with the differential expression of 11 miRNAs; 3 were significantly decreased and 8 were significantly increased in UC tissues. In situ hybridization analysis indicated that miR-192, an miRNA with decreased expression in active UC, was predominantly localized to colonic epithelial cells. Macrophage inflammatory peptide (MIP)-2α, a chemokine expressed by epithelial cells, was identified as a target of miR-192. In colon epithelial cells, induction of MIP-2α expression by tumor necrosis factor-α was accompanied by a concomitant reduction in miR-192 expression and miR-192 was observed to regulate the expression of MIP-2α. Conclusions: These findings expand the known roles of miRNAs, indicating that tissues from patients with UC, and possibly other chronic inflammatory diseases, have altered miRNA expression patterns. These findings also demonstrate that miRNAs regulate colonic epithelial cell-derived chemokine expression.
AB - Background & Aims: Chronic inflammatory bowel diseases such as ulcerative colitis (UC) are associated with differential expression of genes involved in inflammation and tissue remodeling. MicroRNAs (miRNAs), which direct mRNA degradation and translational inhibition, influence a number of disease processes. We examined whether miRNAs are differentially expressed in UC tissues and are associated with expression of genes that regulate inflammation. Methods: miRNA expression was assessed in patients with active UC, inactive UC, Crohn's disease, irritable bowel syndrome, infectious colitis, and microscopic colitis, as well as in healthy subjects by microarray, quantitative reverse transcription-polymerase chain reaction and in situ hybridization analyses. Colonic epithelial cell (HT29) expression of miRNAs was assessed. Regulation of gene expression by miRNAs was assessed by luciferase reporter construct assays and transfection of specific miRNA mimics. Results: Active UC was associated with the differential expression of 11 miRNAs; 3 were significantly decreased and 8 were significantly increased in UC tissues. In situ hybridization analysis indicated that miR-192, an miRNA with decreased expression in active UC, was predominantly localized to colonic epithelial cells. Macrophage inflammatory peptide (MIP)-2α, a chemokine expressed by epithelial cells, was identified as a target of miR-192. In colon epithelial cells, induction of MIP-2α expression by tumor necrosis factor-α was accompanied by a concomitant reduction in miR-192 expression and miR-192 was observed to regulate the expression of MIP-2α. Conclusions: These findings expand the known roles of miRNAs, indicating that tissues from patients with UC, and possibly other chronic inflammatory diseases, have altered miRNA expression patterns. These findings also demonstrate that miRNAs regulate colonic epithelial cell-derived chemokine expression.
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U2 - 10.1053/j.gastro.2008.07.068
DO - 10.1053/j.gastro.2008.07.068
M3 - Article
C2 - 18835392
AN - SCOPUS:55249119513
SN - 0016-5085
VL - 135
SP - 1624-1635.e24
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -