title: Hallmarks of epithelial to mesenchymal transition are detectable in Crohn's disease associated intestinal fibrosis.
abstract: BACKGROUND
  Intestinal fibrosis and subsequent stricture formation represent frequent complications of Crohn's disease (CD). In many organs, fibrosis develops as a result of epithelial to mesenchymal transition (EMT). Recent studies suggested that EMT could be involved in intestinal fibrosis as a result of chronic inflammation. Here, we investigated whether EMT might be involved in stricture formation in CD patients.
  
  
  METHODS
  Human colonic tissue specimens from fibrotic areas of 18 CD and 10 non-IBD control patients were studied. Immunohistochemical staining of CD68 (marker for monocytes/macrophages), transforming growth factor-β1 (TGFβ1), β-catenin, SLUG, E-.cadherin, α-smooth muscle actin and fibroblast activation protein (FAP) were performed using standard techniques.
  
  
  RESULTS
  In fibrotic areas in the intestine of CD patients, a large number of CD68-positive mononuclear cells was detectable suggesting an inflammatory character of the fibrosis. We found stronger expression of TGFβ1, the most powerful driving force for EMT, in and around the fibrotic lesions of CD patients than in non-IBD control patients. In CD patients membrane staining of β-catenin was generally weaker than in control patients and more cells featured nuclear staining indicating transcriptionally active β-catenin, in fibrotic areas. In these regions we also detected nuclear localisation of the transcription factor, SLUG, which has also been implicated in EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high levels of FAP, a marker of reactive fibroblasts.
  
  
  CONCLUSIONS
  We demonstrate the presence of EMT-associated molecules in fibrotic lesions of CD patients. These findings support the hypothesis that EMT might play a role for the development of CD-associated intestinal fibrosis.
authors: Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland ; Zurich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
authors: Michael
authors: M
authors: Scharl
authors: Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors: Nicole
authors: N
authors: Huber
authors: Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors: Silvia
authors: S
authors: Lang
authors: Department of Surgery, Caritas-Hospital St. Josef, Regensburg, Germany.
authors: Alois
authors: A
authors: Fürst
authors: Department of Surgery, Oberschwaben-Klinik, Ravensburg, Germany.
authors: Ekkehard
authors: E
authors: Jehle
authors: Division of Gastroenterology and Hepatology, University Hospital Zürich, Rämistrasse 100, 8091 Zurich, Switzerland ; Zurich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
authors: Gerhard
authors: G
authors: Rogler
keywords: Crohn’s disease; Epithelial-mesenchymal transition; Intestinal fibrosis