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Am J Physiol Lung Cell Mol Physiol 279: L555-L561, 2000;
1040-0605/00 $5.00
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Vol. 279, Issue 3, L555-L561, September 2000

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-2 in fetal rabbit lung

Yuh Fukuda1, Masamichi Ishizaki1, Yasunori Okada2, Motoharu Seiki3, and Nobuaki Yamanaka1

1 Department of Pathology, Nippon Medical School, Tokyo 113-0022; 2 Department of Pathology, Keio University School of Medicine, Tokyo 160-0016; and 3 Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Tokyo 108-0071, Japan

Cell-extracellular matrix interaction and extracellular matrix remodeling are known to be important in fetal lung development. We investigated the localization of matrix metalloproteinases (MMPs) in fetal rabbit lungs. Immunohistochemistry for type IV collagen, MMP-1, MMP-2, MMP-9, membrane type (MT) 1 MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 and in situ hybridization for MMP-9 mRNA were performed. Gelatin zymography and Western blotting for MT1-MMP in lung tissue homogenates were also studied. MMP-1 and MT1-MMP were detected in epithelial cells, and MMP-2 and TIMP-2 were detected in epithelial cells and some mesenchymal cells in each stage. MMP-9 was found in epithelial cells mainly in the late stage. Gelatin zymography revealed that the ratio of active MMP-2 to latent MMP-2 increased dramatically during the course of development. MT1-MMP was detected in tissue homogenates, especially predominant in the late stage. These findings suggest that MMPs and their inhibitors may contribute to the formation of airways and alveoli in fetal lung development and that activated MMP-2 of alveolar epithelial cells may function to provide an extremely wide alveolar surface.

formation of alveoli; type IV collagen; membrane type 1 matrix metalloproteinase; gelatin zymography


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