title: Potential role for SNAIL family transcription factors in the etiology of Crohn's disease-associated fistulae.
abstract: BACKGROUND
  Fistulae represent an important clinical complication of Crohn's disease (CD). The fistula tracts are covered by flat, myofibroblast-like cells with an epithelial origin (transitional cells, TC). We recently demonstrated a role of epithelial mesenchymal transition (EMT) in the pathogenesis of CD-associated fistulae. EMT is associated with an increased migratory and invasive potential of epithelial cells in different tissues. Here we investigated whether cytokines or growth factors as well as EMT-associated SNAIL family transcription factors are expressed in CD fistulae.
  
  
  METHODS
  By immunohistochemistry we analyzed seven perianal fistulae from seven CD and two perianal fistulae from two non-inflammatory bowel disease (IBD) control patients. Hematoxylin and eosin staining or immunohistochemistry for the expression of tumor necrosis factor (TNF), TNF-receptor I (TNF-RI), SNAIL1, SLUG, fibroblast growth factors (FGF) 1, 2, 4, 7, epidermal growth factor (EGF), and TWIST were performed using standard techniques.
  
  
  RESULTS
  Immunohistochemical staining of surgical specimens from CD patients revealed a strong expression of TNF and TNF-RI in and around fistula tracts. While SNAIL1 was also heavily expressed in the nuclei of TC, indicative of transcriptionally active protein, SLUG, FGF-1, and FGF-2 were detected rather in the fibrotic periphery of CD fistulae than in TC. In contrast, we did not detect considerable protein staining for FGF-4 and FGF-7 nor of EGF or the transcription factor, TWIST.
  
  
  CONCLUSIONS
  Our data demonstrate that SNAIL1 and TNF are strongly expressed in TC of CD-associated fistulae. These observations support our previous data and indicate the onset of EMT-associated events in the pathogenesis of CD fistulae.
authors.affiliation: Division of Gastroenterology and Hepatology, Zurich Center for Integrative Human Physiology, University Hospital and University of Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Alois
authors.initials: A
authors.lastname: Fürst
authors.forename: Stefan
authors.initials: S
authors.lastname: Farkas
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Jehle
authors.forename: Theresa
authors.initials: T
authors.lastname: Pesch
authors.forename: Silvia
authors.initials: S
authors.lastname: Kellermeier
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation; D015331:Cohort Studies; D003424:Crohn Disease / Q000150:complications* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D012003:Rectal Fistula / Q000209:etiology* / Q000378:metabolism; D012189:Retrospective Studies; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha