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New Insights Into the Pathogenesis of Inflammatory Bowel Disease: Transcription Factors Analysis in Bioptic Tissues From Pediatric Patients

Pierdomenico, Maria*; Stronati, Laura*; Costanzo, Manuela*; Vitali, Roberta*; Di Nardo, Giovanni; Nuti, Federica; Oliva, Salvatore; Cucchiara, Salvatore; Negroni, Anna*

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3182034d08
Original Articles: Gastroenterology
Abstract

Objectives: Our work is aimed at identifying ex vivo new transcription factors, potentially involved in the pathogenesis of pediatric inflammatory bowel disease (IBD), by using a microarray approach.

Patients and Methods: Microarray, including 84 transcription factors, was performed in inflamed and uninflamed mucosal tissues of pediatric patients with Crohn disease (CD) and in healthy controls. Real-time polymerase chain reaction was used to confirm microarray results on a larger size of CD and patients with ulcerative colitis (UC). Protein expression was evaluated by Western blot assay.

Results: Microarray assay showed 40 genes differentially regulated in the inflamed mucosa and 17 in the uninflamed mucosa of patients with CD as compared with controls. Real-time polymerase chain reaction analysis revealed 10 transcripts in CD and 4 in UC, selected among those with higher differences as compared with healthy controls, significantly overexpressed in the inflamed tissues of patients. Moreover, 4 transcripts in CD and 2 in UC were found significantly upregulated in the uninvolved tissue. A further investigation evidenced an increased protein expression of activating transcription factor 3 and hypoxia-inducible transcription factor-1α in patients with CD as well as in Caco2 cell line stimulated by cytokines and hypoxia.

Conclusions: The present study shows an evident upregulation of several transcription factors in the inflamed and uninflamed mucosa of children with IBD, suggesting that the inflammatory process is somehow activated at molecular levels even in the macroscopically normal mucosa of patients. A differential pattern of gene expression between CD and UC indicates distinct molecular mechanisms underlying the pathogenesis of 2 diseases. Finally, activating transcription factor 3 and hypoxia-inducible transcription factor-1α are proposed as new transcription factors potentially involved in the onset and maintenance of IBD.

Author Information

*ENEA, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Italy

Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University Hospital Umberto I, Rome, Italy.

Received 13 May, 2010

Accepted 20 October, 2010

Address correspondence and reprint requests to Anna Negroni, PhD, Section of Toxicology and Biomedical Sciences, Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Via Anguillarese 301, 00123 Rome, Italy (e-mail: anna.negroni@enea.it).

The authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN