title: Cellular sources of MMP-7, MMP-13 and MMP-28 in ulcerative colitis.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are considered the predominant proteases in the pathogenesis of mucosal ulcerations associated with inflammatory bowel disease (IBD). Whether the malignancy associated MMP-7 and MMP-13 or the recently cloned MMP-28 convey a certain meaning for intestinal homeostasis and pathogenesis of IBD is currently unknown. We therefore set off to analyze regulation patterns and cellular origins of these MMPs in mucosal tissues of patients with ulcerative colitis (UC).
  
  
  METHODS
  Biopsy samples of affected and healthy tissues were obtained from 35 Norwegian patients with UC. RNA was quantified by quantitative real-time polymerase chain reaction to study MMP gene expression in both pathological and healthy mucosal specimens. Cellular origins were determined by immunohistology using surrogate markers for inflammation, neovascularization, and epithelial structures. Protein expression of MMP-7 and MMP-13 was quantified using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  MMP-7 and MMP-13 gene expression was significantly increased in UC affected colonic mucosa whereas MMP-28 showed a decreased expression in inflamed mucosa. Endothelial cells and infiltrating leukocytes were identified as the major cellular sources of MMP-7 and MMP-13 in UC. Enterocytes represented the major cellular source of MMP-28 in healthy and inflamed mucosa.
  
  
  CONCLUSIONS
  MMP-7 and MMP-13 expression in inflammatory and endothelial cells indicate a role of these MMPs for both colitis associated neoangiogenesis and inflammatory changes. Decreased MMP-28 expression in UC is most likely the result of colitis associated epithelial destruction and loss of cryptal architecture.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.forename: Martin
authors.initials: M
authors.lastname: Roderfeld
authors.forename: Jörg Michael
authors.initials: JM
authors.lastname: Halwe
authors.forename: Annette
authors.initials: A
authors.lastname: Tschuschner
authors.forename: Elke
authors.initials: E
authors.lastname: Roeb
authors.forename: Jürgen
authors.initials: J
authors.lastname: Graf
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000235:genetics*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; C424663:MMP28 protein, human; D053509:Matrix Metalloproteinase 13; D053505:Matrix Metalloproteinases, Secreted; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7