Published online Jul 14, 2016. doi: 10.3748/wjg.v22.i26.6027
Peer-review started: March 26, 2016
First decision: May 12, 2016
Revised: June 2, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: July 14, 2016
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-β (TGF-β) 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-β (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-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-β 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-β plays an important role in the regulation of the expression of these miRs.
Core tip: Recent evidence suggests that besides the genetic basis, epigenetic factors including microRNAs (miRs) also act as potent inflammatory modulators during the pathogenesis of inflammatory bowel disease. MiR expression in the upper-gastrointestinal tract of pediatric patients with Crohn’s disease (CD) has not yet been analyzed. Moreover, the relation of transforming growth factor-β, playing a prominent role in the pathomechanism of CD, to miRs in this setting is also unknown. The description of precise miR patterns specific for the different segments of the gastrointestinal tract may contribute to the introduction of novel diagnostic markers and to the identification of potential therapeutic targets.