Deletion of aquaporin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa.
Deletion of aquaporin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa.
复制标题
水通道蛋白5的缺失会加重铜绿假单胞菌引起的急性肺损伤。
DOI：
10.1097/ta.0b013e3182128528
复制
发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Song YL
中科院分区：
文献类型：
--
作者：
Bai CX;Zhang ZQ;Song YL
背景
水通道蛋白（Aquaporin，AQP）是一种促进水渗透转运的膜蛋白。水通道蛋白5（AQP 5）表达于具有高渗透性水渗透性的顶膜I型肺泡上皮。肺泡灌洗液或牵张刺激可显著上调AQP 5的表达，提示AQP 5可能在维持上皮屏障功能中发挥作用。铜绿假单胞菌（PA）是一种常见的革兰氏阴性菌，常从通气相关性肺炎患者中分离出来，破坏肺泡和气道上皮细胞，随后导致血液传播。本研究假设AQP 5在PA诱导的急性肺损伤中可能具有保护作用，AQP 5的缺失可能导致肺损伤加重。
方法
采用PA（1 × 10（6）集落形成单位）诱导野生型和AQP 5基因敲除小鼠肺损伤模型，分别于2 h和6 h后取血和肺组织培养检测血播散，取支气管肺泡灌洗液和肺组织进行组织学分析。评价肺损伤评估、湿/干重比、蛋白渗漏和伊文思蓝染料外渗的肺屏障功能。
结果
AQP 5缺失导致PA感染时细菌血液播散增加，加重肺损伤，AQP 5缺失还导致肺粘蛋白产生减少。此外，AQP 5缺乏显示PA感染前后肺中丝裂原活化蛋白激酶和核因子-κ B通路的活化下降。
结论
我们的数据表明，AQP 5在维持肺屏障功能对抗PA感染中起保护作用。
BACKGROUND
Aquaporin (AQP) is a membrane protein that facilitates osmotic water transport. Aquaporin 5 (AQP5) expresses at type I alveolar epithelia of apical membrane that confers high osmotic water permeability. Osmosis or stretch challenge in alveoli significantly up-regulates AQP5 expression, which suggests that AQP5 may play a role in the maintenance of epithelia barrier function. Pseudomonas aeruginosa (PA), a leading gram-negative bacterial frequently isolated from ventilation-associated pneumonia patients, disrupts alveolar and airway epithelial cells and subsequently leads to blood dissemination. In this study, we hypothesized that AQP5 might be protective in acute lung injury induced by PA, and deletion of AQP5 might lead to aggravated lung injury.
METHODS
Lung injury model was induced by intratracheal instillation of PA (1 × 10(6) colony-forming unit) in wild-type and AQP5 knockout mice, 2 hours and 6 hours later, blood and lung lysate were cultured to detect blood dissemination, bronchoalveolar lavage fluid and lung tissue were collected for histology analysis. Lung injury assessment, wet/dry weight ratio, protein leakage, and Evan's blue dye extravasation were evaluated for pulmonary barrier function.
RESULTS
AQP5 deficiency led to increased bacterial blood dissemination and aggravated lung injury during PA infection, and AQP5 deletion also reduced mucin production in lung. Moreover, AQP5 deficiency showed declined activation of mitogen-activated protein kinase and nuclear factor-kappa B pathways in lungs before and after PA infection.
CONCLUSION
Our data demonstrated that AQP5 plays a protective role in the maintenance of pulmonary barrier function against PA infection.
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DOI：
10.1164/ajrccm.162.5.9906096
发表时间：
2000-11-01
影响因子：
24.7
作者：
Suga, M;Iyonaga, K;Ando, M
通讯作者：
Ando, M
DOI：
10.1097/00132586-200202000-00005
发表时间：
2003
期刊：
--
影响因子：
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作者：
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DOI：
10.1093/med/9780190467654.003.0010
发表时间：
2018-02
期刊：
--
影响因子：
--
作者：
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通讯作者：
A. Ward;R. M. Pino
影响因子：
15.9
作者：
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通讯作者：
Verkman, AS
影响因子：
64.8
作者：
Rius, Jordi;Guma, Monica;Karin, Michael
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Karin, Michael