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). Material and 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.

Key Words::

• Inflammatory bowel disease
• matrix metalloproteinases
• tissue inhibitors of metalloproteinases
• ulcerative colitis

Acknowledgements

This work was performed at the Department of Internal Medicine, Justus-Liebig University Giessen, and supported by grants from the Deutsche Forschungsgemeinschaft (RO 957/6-1 and RO 957/7-1) and ZooMAP (Bundesministerium für Bildung und Forschung, BMBF). Dr. Timo Rath has received grants for young researchers (Anschubfinanzierung) from the Justus-Liebig-University Giessen.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.