Increased duodenal expression of mi R-146a and-155 in pediatric Crohn’s disease

• Published in: 世界胃肠病学杂志：英文版 2016 (26), p.6027-6035
• Main Author: Dániel Sz?cs Nóra Judit Béres Réka Rokonay Kriszta Boros Katalin Borka Zoltán Kiss András Arató Attila J Szabó ádám Vannay Erna Sziksz Csaba Bereczki Gábor Veres
• Format: Article
• Language: English
• Subjects: bowel; disease; Crohn’s; disease; Pediatric; Micro; factor-β; growth; Inflammatory; RNAs; transforming
• ISSN: 1007-9327; 2219-2840

AIM: To evaluate the role of micro RNA(mi R)-146 a,-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 mi Rs 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 mi R-146 a,-155 and-122 was determined by realtime polymerase-chain reaction(PCR). The expression of the above mi Rs 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 mi R-146 a 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 mi R-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 mi R-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of mi R-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 mi R-146a(TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, p ≤ 0.01) and mi R-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 mi R-122.CONCLUSION: The elevated expression of mi R-146 a and-155 in the inflamed duodenal mucosa of CD patients suggests the role of these mi Rs in the pathomechanism of inflammatory bowel disease. Antiinflammatory TGF-β plays an important role in the regulation of the expression of these mi Rs.