Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury
Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury
复制标题
DOI：
10.4049/jimmunol.174.11.7250
复制
发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Yan, C
中科院分区：
文献类型：
--
作者：
Lian, XM;Qin, YL;Yan, C
急性肺损伤是患者吸入高浓度氧气治疗的副作用。这种效应背后的分子机制还知之甚少。在这项研究中，我们报告了在多西环素控制的双转基因小鼠系统的呼吸道上皮细胞中过表达STAT3的构成活性形式Stat3C，以保护肺免受高氧引起的炎症和损伤。在这个小鼠品系中，50%的转基因小鼠在暴露于95%氧气的第7天存活，而野生型小鼠的存活率为0%。STAT3C的过度表达延缓了急性毛细血管渗漏和中性粒细胞渗入肺泡区。这种保护作用至少部分是通过抑制高氧诱导中性粒细胞和肺泡内停留细胞合成和释放基质金属蛋白酶(MMP9)和MMP12来实现的。在一些MMP9(-/-)小鼠中，观察到在高氧条件下存活时间延长。这一发现支持了这样一个概念，即STAT3通路的激活在防止高氧诱导的肺部炎症和损伤方面发挥了作用。
Acute lung injury is a side effect of therapy with a high concentration of inspired oxygen in patients. The molecular mechanism underlining this effect is poorly understood. In this study, we report that overexpression of Stat3C, a constitutive active form of STAT3, in respiratory epithelial cells of a doxycycline-controlled double-transgenic mouse system protects lung from inflammation and injury caused by hyperoxia. In this mouse line, > 50% of transgenic mice survived exposure to 95% oxygen at day 7, compared with 0% survival of wild-type mice. Overexpression of STAT3C delays acute capillary leakage and neutrophil infiltration into the alveolar region. This protection is mediated at least partially through inhibition of hyperoxia-induced synthesis and release of matrix metalloproteinase (MMP)-9 and MMP-12 by neutrophils and alveolar resident cells. In some MMP-9(-/-) mice, prolonged survival was observed under hyperoxic condition. The finding supports a concept that activation of the Stat3 pathway plays a role to prevent hyperoxia-induced inflammation and injury in the lung.