Role of matrix metalloprotease-9 in hyperoxic injury in developing lung
| Autor: | Amy Simon, Anne Chetty, Gong-Jie Cao, Mariano Severgnini, Heber C. Nielsen, Rod R. Warburton |
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| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Physiology Alveolar Epithelium Hyperoxia Lung injury Mice Physiology (medical) medicine Animals Respiratory system Lung Respiratory Distress Syndrome Tropoelastin biology business.industry Body Weight Articles Cell Biology respiratory system medicine.disease Elastin Respiratory Function Tests respiratory tract diseases Pulmonary Alveoli medicine.anatomical_structure Animals Newborn Matrix Metalloproteinase 9 Bronchopulmonary dysplasia biology.protein medicine.symptom business |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 295:L584-L592 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00441.2007 |
| Popis: | Matrix metalloprotease-9 (MMP-9) is increased in lung injury following hyperoxia exposure in neonatal mice, in association with impaired alveolar development. We studied the role of MMP-9 in the mechanism of hyperoxia-induced functional and histological changes in neonatal mouse lung. Reduced alveolarization with remodeling of ECM is a major morbidity component of oxidant injury in developing lung. MMP-9 mediates oxidant injury in developing lung causing altered lung remodeling. Five-day-old neonatal wild-type (WT) and MMP-9 (−/−) mice were exposed to hyperoxia for 8 days. The lungs were inflation fixed, and sections were examined for morphometry. The mean linear intercept and alveolar counts were evaluated. Immunohistochemistry for MMP-9 and elastin was performed. MMP-2, MMP-9, type I collagen, and tropoelastin were measured by Western blot analysis. Lung quasistatic compliance was studied in anaesthetized mice. MMP-2 and MMP-9 were significantly increased in lungs of WT mice exposed to hyperoxia compared with controls. Immunohistochemistry showed an increase in MMP-9 in mesenchyme and alveolar epithelium of hyperoxic lungs. The lungs of hyperoxia-exposed WT mice had less gas exchange surface area and were less compliant compared with room air-exposed WT and hyperoxia-exposed MMP-9 (−/−) mice. Type I collagen and tropoelastin were increased in hyperoxia-exposed WT with aberrant elastin staining. These changes were ameliorated in hyperoxia-exposed MMP-9 (−/−) mice. MMP-9 plays an important role in the structural changes consequent to oxygen-induced lung injury. Blocking MMP-9 activity may lead to novel therapeutic approaches in preventing bronchopulmonary dysplasia. |
| Databáze: | OpenAIRE |
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