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Developmentally regulated expression of matrix metalloproteinases during fetal rat colon morphogenesis

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To investigate the role of matrix metalloproteinases (MMPs) during gastrointestinal tract development, the expression of gelatinases (MMP-2 and MMP-9) was investigated during fetal rat colon morphogenesis. Fetal rat colons were separated into epithelial and mesenchymal fractions without cross contamination using a chelating agent and a dissecting microscope. Gelatinase activity measured using fluorescently labeled gelatin was higher in the mesenchymal than in the epithelial fraction; the developmental profile revealed that, in both fractions, gelatinase activity was enhanced during colon morphogenesis. During colonic gland formation, there was prominent MMP-2 activity, elevated MMP-2 mRNA expression, and an increase in the level of the active form of MMP-2 in the mesenchymal fraction. The mRNA expression of the tissue inhibitor of metalloproteinase 2 corresponded with an elevation in the level of the active form of MMP-2; the mRNA expression of the cell surface activator of MMP-2, membrane type matrix metalloproteinase 1, did not increase significantly. MMP-9 activity was low; only the pro-form was observed in the epithelial fraction at the end of fetal life. These results suggest that, during colon morphogenesis, MMP activity is under strict spatio-temporal control, and that the activity of MMP-2, which is regulated at both the transcriptional and proteolytic activation levels, is very much involved in rat colon morphogenesis.

Keywords: colon; development; extracellular matrix; matrix metalloproteinase; morphogenesis

Document Type: Research Article


Affiliations: 1: Division of Gastroenterology and Hepatology, Department of Internal Medicine (Ohmori), School of Medicine, Faculty of Medicine, Toho University School of Medicine, Tokyo 143-8540, Japan, 2: Second Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama-city, Wakayama 641-0012, Japan, 3: Department of Gastroenterology, Toshiba General Hospital, Tokyo 140-8522, Japan, 4: Department of Gastroenterology, Faculty of Medicine, the University of Tokyo, Tokyo 113-0033, Japan, 5: Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo 113-8519, Japan, 6: Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan

Publication date: January 1, 2008

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