MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α

Feng Wu, Michelle Zikusoka, Anil Trindade, Themistocles Dassopoulos, Mary L. Harris, Theodore M. Bayless, Steven R. Brant, Shukti Chakravarti, John H. Kwon

Research output: Contribution to journalArticle

331 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalGastroenterology
Volume135
Issue number5
DOIs
StatePublished - Nov 1 2008

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MicroRNAs
Ulcerative Colitis
Macrophages
Peptides
Epithelial Cells
Chemokines
In Situ Hybridization
Microscopic Colitis
Inflammation
Gene Expression
Irritable Bowel Syndrome
RNA Stability
Gene Expression Regulation
Colitis
Luciferases
Inflammatory Bowel Diseases
Crohn Disease
Reverse Transcription
Transfection
Healthy Volunteers

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Wu, F., Zikusoka, M., Trindade, A., Dassopoulos, T., Harris, M. L., Bayless, T. M., ... Kwon, J. H. (2008). MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α. Gastroenterology, 135(5). https://doi.org/10.1053/j.gastro.2008.07.068

MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α. / Wu, Feng; Zikusoka, Michelle; Trindade, Anil; Dassopoulos, Themistocles; Harris, Mary L.; Bayless, Theodore M.; Brant, Steven R.; Chakravarti, Shukti; Kwon, John H.

In: Gastroenterology, Vol. 135, No. 5, 01.11.2008.

Research output: Contribution to journalArticle

Wu, F, Zikusoka, M, Trindade, A, Dassopoulos, T, Harris, ML, Bayless, TM, Brant, SR, Chakravarti, S & Kwon, JH 2008, 'MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α', Gastroenterology, vol. 135, no. 5. https://doi.org/10.1053/j.gastro.2008.07.068
Wu, Feng ; Zikusoka, Michelle ; Trindade, Anil ; Dassopoulos, Themistocles ; Harris, Mary L. ; Bayless, Theodore M. ; Brant, Steven R. ; Chakravarti, Shukti ; Kwon, John H. / MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2α. In: Gastroenterology. 2008 ; Vol. 135, No. 5.
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abstract = "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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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.

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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.

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