Cellular sources of MMP-7, MMP-13 and MMP-28 in ulcerative colitis.
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.
Rath
Timo
T
Department of Internal Medicine, Division of Gastroenterology, Justus-Liebig-University Giessen, Giessen, Germany.
Roderfeld
Martin
M
Halwe
Jörg Michael
JM
Tschuschner
Annette
A
Roeb
Elke
E
Graf
Jürgen
J
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
D015415:Biomarkers; C424663:MMP28 protein, human; D053509:Matrix Metalloproteinase 13; D053505:Matrix Metalloproteinases, Secreted; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7