title: Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn's disease: relevance to local angiotensin II system.
abstract: BACKGROUND
  Intestinal stricture lesions in Crohn's disease are characterized as submucosal fibromuscular accumulation. There has been a controversy about whether the fibrogenic cells in stricture lesions in Crohn's disease originate from a smooth muscle cell or a fibroblast lineage. In the present study, we aimed to elucidate: (1) the origin of the fibrogenic cells in stricture lesions; and (2) the roles of the local angiotensin II system, including mast cell chymase, in stricture formation.
  
  
  METHODS
  Methanol-Carnoy's-fixed colonic tissues, obtained from the stricture sites of 18 patients with Crohn's disease, were analyzed by immunostaining for vimentin, smooth muscle actin (1A4 and CGA7), angiotensin II type-1 receptor, angiotensin II-converting enzyme, and mast cell tryptase and chymase. As controls, unaffected (normal) portions of 11 colonic tumor specimens were also investigated.
  
  
  RESULTS
  Submucosal fibromuscular accumulation was seen in every stricture lesion. The majority of mesenchymal cells accumulated in the stricture lesions were moderately differentiated intestinal smooth muscle cells [vimentin(+), 1A4(+), and CGA7(+)]. Moreover, occasional intestinal smooth muscle cells in the muscular layers, adjacent to the site of the submucosal fibromuscular response, showed distinct positivity for vimentin, indicating phenotypic modulation toward an immature, or dedifferentiated state. These smooth muscle cells accumulated in the stricture lesions were positive for angiotensin II type-1 receptor. Abundant chymase-positive mast cells were distributed in these lesions.
  
  
  CONCLUSIONS
  These results suggest that the proliferation and migration of moderately differentiated intestinal smooth muscle cells from the muscular layers are the major pathological mechanisms in stricture formation in Crohn's disease, and the angiotensin II system is involved in this process.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Suekane
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Junko
authors.initials: J
authors.lastname: Arimoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iwasa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Sugama
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kayo
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugioka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Maeda
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D053818:Chymases / Q000378:metabolism; D003251:Constriction, Pathologic / Q000473:pathology*; D003424:Crohn Disease / Q000473:pathology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010641:Phenotype
chemical_list: D000804:Angiotensin II; D053818:Chymases