title: Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn's disease.
abstract: BACKGROUND
  The pathogenesis of fistulae in Crohn's disease (CD) patients is barely understood. We recently showed that more than two-thirds of CD fistulae are covered with flat, mesenchymal-like cells (transitional cells [TC]) forming a patchy basement membrane. Epithelial-to-mesenchymal transition (EMT) is a process of reprogramming epithelial cells, allowing them to migrate more effectively and giving epithelial cells an "invasive" potential. EMT has been suggested to be crucial in fibrosis found in different tissues and diseases. We therefore investigated whether EMT could be involved in the pathogenesis of fistulae formation in CD.
  
  
  METHODS
  In all, 18 perianal fistulae, 2 enteroenteric, and 1 enterovesical fistulae from 17 CD patients were analyzed. In addition 2 perianal fistulae of non-CD patients were studied. Hematoxylin and eosin staining, immunohistochemistry for the expression of cytokeratins 8 and 20, beta6-integrin, E-cadherin, beta-catenin, vimentin, and TGF-beta1 and 2 were performed according to standard techniques.
  
  
  RESULTS
  The TC covering perianal or enteroenteric fistulae were strongly positive for cytokeratins 8 and 20 but negative for vimentin, indicating their epithelial origin. beta6-Integrin and TGF-beta had the highest staining intensities in the transitional zone between the epithelium and the TC. Expression of junctional proteins such as E-cadherin was reduced in TC as compared to regular fistulae epithelium. In addition, a translocation of beta-catenin from the membrane to the cytoplasm was observed.
  
  
  CONCLUSIONS
  Our data for the first time indicate an expression pattern of epithelial and mesenchymal markers in TC associated with fistulae formation that is characteristic for EMT. Studying the pathways of EMT during intestinal fistulae formation may help to develop new therapeutic strategies.
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Christian
authors.initials: C
authors.lastname: Rohrmeier
authors.forename: Richard
authors.initials: R
authors.lastname: Bates
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Florian
authors.initials: F
authors.lastname: Rieder
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Ulrike
authors.initials: U
authors.lastname: Strauch
authors.forename: Stefan
authors.initials: S
authors.lastname: Farkas
authors.forename: Alois
authors.initials: A
authors.lastname: Fürst
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D017577:Cutaneous Fistula / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007412:Intestinal Fistula / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000473:pathology*; D008875:Middle Aged; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D015820:Cadherins