Stat-3 is required for pulmonary homeostasis during hyperoxia
Stat-3 is required for pulmonary homeostasis during hyperoxia
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DOI：
10.1172/jci200419491
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发表时间：
2004-01-01
影响因子：
15.9
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Hokuto, I;Ikegami, M;Whitsett, JA
急性肺损伤综合征仍然是成人和儿童发病率和死亡率的常见原因。在肺损伤期间维持肺内环境稳定的细胞和生理机制仍然知之甚少。在本研究中，选择性地删除的Stat-3基因在呼吸道上皮细胞的条件下表达的Cre重组酶的表面活性蛋白C基因启动子的控制下。呼吸道上皮细胞中Stat-3的细胞选择性缺失不会改变出生前肺形态发生或出生后肺功能。然而，成年Stat-3缺失小鼠暴露于95%的氧气导致更快进行性肺损伤，与肺泡毛细血管渗漏和急性呼吸窘迫相关。在Stat-3缺失的小鼠中，上皮细胞损伤和炎症反应增加。肺泡灌洗液中表面活性蛋白和脂质减少或不存在。外源性表面活性蛋白B的肠内治疗改善了Stat-3缺失小鼠在高氧期间的存活率和肺组织学。Stat-3在呼吸道上皮细胞中的表达不是肺形成所必需的，但在氧损伤期间维持表面活性物质稳态和肺功能中起关键作用。
Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3-deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3-deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3-deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.