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

Yuh Fukuda, Masamichi Ishizaki, Yasunori Okada, Motoharu Seiki, Nobuaki Yamanaka

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64 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)L555-L561
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 23-3
Publication statusPublished - 2000 Oct 4


  • Formation of alveoli
  • Gelatin zymography
  • Membrane type 1 matrix metalloproteinase
  • Type IV collagen

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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