Increased duodenal expression of miR-146a and -155 in pediatric Crohn's disease.
World J Gastroenterol
; 22(26): 6027-35, 2016 Jul 14.
Article
em En
| MEDLINE
| ID: mdl-27468194
ABSTRACT
AIM:
To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn's disease (CD) and the effect of transforming growth factor-ß (TGF-ß) on these miRs in duodenal epithelial and fibroblast cells.METHODS:
Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed n = 10) and intact (CD intact n = 10) duodenal mucosa of pediatric CD patients and control children (C n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-ß (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS:
Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed 3.21 ± 0.50 vs CD intact 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed 3.21 ± 0.50 vs C 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed 4.87 ± 1.02 vs CONTROL 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-ß treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-ß 0.7 ± 0.083 vs CONTROL 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-ß 0.67 ± 0.04 vs CONTROL 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-ß 0.72 ± 0.09 vs CONTROL 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-ß treatment did not influence the expression of miR-122.CONCLUSION:
The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-ß plays an important role in the regulation of the expression of these miRs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
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MicroRNAs
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Duodeno
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Mucosa Intestinal
Limite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
World J Gastroenterol
Ano de publicação:
2016
Tipo de documento:
Article