title: Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn mice.
abstract: Cathepsin K (CatK) is a potent collagenase and elastase and may be involved in the development of neonatal bronchopulmonary dysplasia. The authors evaluated the effects of CatK deletion on neonatal lung development and response to prolonged hyperoxic challenge. CatK deficiency resulted in thinner alveolar walls than wild-type littermates on postnatal day (PN) 7. However, no morphological difference could be detected between CatK-deficient and control groups on PN 14. Exposure to 90% oxygen for 7 days after birth caused intensive CatK expression in the bronchial epithelium and alveolar macrophages of wild-type mice. Hyperoxia caused fatal respiratory distress in both groups of mice. However, whereas ∼20% of wild-type mice survived for 2 weeks in hyperoxia, all CatK-deficient mice died within the first 9 postnatal days. Hyperoxia-exposed lungs of CatK-deficient mice contained high number of macrophages and multinucleated giant cells and had increased content of reduced glutathione, indicating intensified pulmonary oxidative stress. These results suggest that CatK is involved in pulmonary development and it may be an important host-defence protease in the oxygen-stressed newborn lung.
authors: Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland. jonni.knaapi@utu.fi
authors: Jonni
authors: J
authors: Knaapi
authors: Heikki
authors: H
authors: Lukkarinen
authors: Riku
authors: R
authors: Kiviranta
authors: Eero
authors: E
authors: Vuorio
authors: Pekka
authors: P
authors: Kääpä
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D056657:Cathepsin K / Q000172:deficiency* / Q000276:immunology / Q000502:physiology*; D018496:Hyperoxia / Q000150:complications*; D008168:Lung / Q000254:growth & development / Q000473:pathology; D055370:Lung Injury / Q000209:etiology*; D016676:Macrophages, Alveolar; D051379:Mice; D018384:Oxidative Stress; D011650:Pulmonary Alveoli
chemical_list: D056657:Cathepsin K; C534132:Ctsk protein, mouse