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/jci19491
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
I. Hokuto;M. Ikegami;Mitsuhiro Yoshida;K. Takeda;S. Akira;A. Perl;W. Hull;S. Wert;J. Whitsett
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文献类型：
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作者：
I. Hokuto;M. Ikegami;Mitsuhiro Yoshida;K. Takeda;S. Akira;A. Perl;W. Hull;S. Wert;J. Whitsett
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。在肺损伤过程中维持肺内环境稳定的细胞和生理机制尚不清楚。在本研究中，通过在表面活性蛋白C基因启动子的控制下有条件地表达Cre重组酶，在呼吸道上皮细胞中选择性地缺失了Stat-3基因。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缺失小鼠暴露在95%的氧气中会导致与肺泡毛细血管渗漏和急性呼吸窘迫相关的更迅速的进行性肺损伤。Stat-3缺失的小鼠上皮细胞损伤和炎症反应增加。肺泡灌洗材料中表面活性物质蛋白和脂类减少或缺失。气管内应用外源性表面活性蛋白B可改善高氧期间Stat-3基因缺失小鼠的存活率和肺组织学。肺上皮细胞中Stat-3的表达不是肺形成所必需的，但在氧损伤时维持肺表面活性物质的动态平衡和肺功能方面起着关键作用。
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.