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New insights into the pathogenesis of inflammatory bowel disease: Transcription factors analysis in bioptic tissues from pediatric patients

TitleNew insights into the pathogenesis of inflammatory bowel disease: Transcription factors analysis in bioptic tissues from pediatric patients
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2011
AuthorsPierdomenico, Maria, Stronati L., Costanzo Manuela, Vitali Roberta, Di Nardo G., Nuti F., Oliva S., Cucchiara S., and Negroni Anna
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume52
Pagination271-279
ISSN02772116
Keywordsactivating transcription factor 3, adolescent, article, azathioprine, Biopsy, cell strain CACO 2, Child, clinical trial, colitis, controlled study, corticosteroid, Crohn disease, cytokine, enteritis, ex vivo study, Female, gene control, Gene expression, gene expression regulation, gene identification, human, human cell, Humans, hypoxia, hypoxia inducible factor 1alpha, Infant, inflammation, Intestinal Mucosa, low drug dose, male, mesalazine, methylprednisolone, microarray analysis, mucosa, Oligonucleotide Array Sequence Analysis, pediatrics, Polymerase Chain Reaction, Preschool, preschool child, priority journal, protein expression, real time polymerase chain reaction, Reference Values, school child, Transcription Factors, Ulcerative, ulcerative colitis, Up-Regulation, upregulation
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. © 2011 Lippincott Williams & Wilkins, Inc.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-79952316793&doi=10.1097%2fMPG.0b013e3182034d08&partnerID=40&md5=7b4bbc5cf6fe9359303c39a7759e5904
DOI10.1097/MPG.0b013e3182034d08
Citation KeyPierdomenico2011271