Membrane-type 1 matrix metalloproteinase is required for normal alveolar development

Jeffrey J. Atkinson, Kenn Holmbeck, Susan Yamada, Henning Birkedal-Hansen, William C. Parks, Robert M. Senior

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Abstract

Matrix metalloproteinases (MMPs) are expressed during lung development, but their role may be limited, as mice deficient in MMP-3, 7, 9, or 12 develop a normal adult lung. Because membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in the developing lung epithelium, we examined the lung structure of MT1-MMP-deficient (-/-) mice. Branching morphogenesis was normal, but alveolar development was abnormal in the MT1-MMP-/- lungs with 40% less alveolar surface area at 1 month (P < 0.01). MT1-MMP-/- airways and alveoli had an abnormal ultrastructural appearance, but epithelial cell differentiation markers were distributed similarly in both strains. There was no evidence of excess extracellular matrix deposition or inflammation at the time points examined. In contrast, by adulthood MMP-2-/- mice had normal alveolar size and structure, indicating normal alveolar development was not dependent on the ability of MT1-MMP to activate pro-MMP-2. These data indicate that MT1-MMP is required for normal lung development.

Original languageEnglish
Pages (from-to)1079-1090
Number of pages12
JournalDevelopmental Dynamics
Volume232
Issue number4
DOIs
StatePublished - Apr 2005

Keywords

  • Alveolar
  • Clara
  • Development
  • Emphysema
  • Lung
  • Matrix metalloproteinase
  • Pore

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    Atkinson, J. J., Holmbeck, K., Yamada, S., Birkedal-Hansen, H., Parks, W. C., & Senior, R. M. (2005). Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Developmental Dynamics, 232(4), 1079-1090. https://doi.org/10.1002/dvdy.20267