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Am J Physiol Lung Cell Mol Physiol 283: L747-L754, 2002. First published May 17, 2002; doi:10.1152/ajplung.00415.2001
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Vol. 283, Issue 4, L747-L754, October 2002

Dynamics of metalloproteinase-2 and -9, TGF-beta , and uPA activities during normoxic vs. hyperoxic alveolarization

S. Buckley and D. Warburton

Developmental Biology Program, Childrens Hospital Los Angeles Research Institute, Los Angeles, California 90027

The final stage of lung development, alveolarization, continues after birth in humans and rodents. Clinical interventions, such as oxygen therapy, in the first week of life can adversely impact alveolar formation. We compared alveolarization in the rat neonate under normal vs. hyperoxic conditions, examining gelatinase, transforming growth factor (TGF)-beta , and the protease urokinase-type plasminogen activator (uPA) activities in whole lung and cultured type II alveolar epithelial cells (AEC2). The dynamic induction of gelatinase, TGF-beta , and uPA activities seen in neonatal lungs during the first days of life was significantly impacted by hyperoxia. In whole lung, gelatinase and TGF-beta activities were increased, while uPA activity was decreased. At the level of the epithelium, AEC2 isolated from hyperoxic rat pups early in life secreted less active TGF-beta , less active gelatinases, and less active uPA than control neonatal AEC2. AEC2 from hyperoxic pups also expressed increased levels of proliferating cell nuclear antigen early in life compared with control neonatal AEC2, suggesting that oxygen-induced proliferation and/or repair were occurring. The developmental profile of neonatal lung was perturbed within a day of initiating oxygen treatment, suggesting that putative palliative treatments should be coadministered with oxygen therapy.

matrix metalloproteinases; active transforming growth factor-beta ; gelatinase A; gelatinase B; urokinase-type plasminogen activator; type II alveolar epithelial cells


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