Knaapi Jonni, Lukkarinen Heikki, Kiviranta Riku, Vuorio Eero, Kääpä Pekka
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland.
Exp Lung Res. 2011 Sep;37(7):408-18. doi: 10.3109/01902148.2011.581738. Epub 2011 Jul 1.
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.
组织蛋白酶K（CatK）是一种强效的胶原酶和弹性蛋白酶，可能参与新生儿支气管肺发育不良的发生发展。作者评估了CatK基因缺失对新生儿肺发育以及对长时间高氧刺激反应的影响。在出生后第7天（PN7），CatK基因缺失的小鼠肺泡壁比野生型同窝小鼠更薄。然而，在PN14时，未检测到CatK基因缺失组与对照组之间存在形态学差异。出生后暴露于90%氧气环境7天，导致野生型小鼠支气管上皮和肺泡巨噬细胞中CatK表达增强。高氧环境导致两组小鼠均出现致命的呼吸窘迫。然而，约20%的野生型小鼠在高氧环境中存活了2周，而所有CatK基因缺失的小鼠在出生后的前9天内死亡。CatK基因缺失且暴露于高氧环境的小鼠肺中含有大量巨噬细胞和多核巨细胞，且还原型谷胱甘肽含量增加，表明肺部氧化应激增强。这些结果表明，CatK参与肺发育，并且可能是氧应激新生儿肺中一种重要的宿主防御蛋白酶。
