title: Increased duodenal expression of miR-146a and -155 in pediatric Crohn's disease.
abstract: OBJECTIVE
  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
  
  
  METHODS
  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
  
  
  METHODS
  1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs
  
  
  METHODS
  1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Dániel
authors.initials: D
authors.lastname: Szűcs
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Nóra Judit
authors.initials: NJ
authors.lastname: Béres
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Réka
authors.initials: R
authors.lastname: Rokonay
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Kriszta
authors.initials: K
authors.lastname: Boros
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Borka
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kiss
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Arató
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabó
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Vannay
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Erna
authors.initials: E
authors.lastname: Sziksz
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Bereczki
authors.affiliation: Dániel Szűcs, Csaba Bereczki, Department of Pediatrics and Pediatric Health Care Center, University of Szeged, H-6725 Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
mesh_terms: D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D004386:Duodenum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C531907:MIRN122 microRNA, human; C542542:MIRN146 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016212:Transforming Growth Factor beta
keywords: Crohn’s disease; Inflammatory bowel disease; MicroRNAs; Pediatric; Transforming growth factor-β