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

TY - JOUR

T1 - Membrane-type 1 matrix metalloproteinase is required for normal alveolar development

AU - Atkinson, Jeffrey J

AU - Holmbeck, Kenn

AU - Yamada, Susan

AU - Birkedal-Hansen, Henning

AU - Parks, William C

AU - Senior, Robert M

N1 - Copyright 2005 Wiley-Liss, Inc.

PY - 2005/4

Y1 - 2005/4

N2 - 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.

AB - 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.

KW - Animals

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases/deficiency

KW - Mice

KW - Mice, Knockout

KW - Microscopy, Electron, Scanning

KW - Pulmonary Alveoli/embryology

U2 - 10.1002/dvdy.20267

DO - 10.1002/dvdy.20267

M3 - Journal article

C2 - 15739229

SN - 1058-8388

VL - 232

SP - 1079

EP - 1090

JO - Developmental Dynamics

JF - Developmental Dynamics

IS - 4

ER -