17β-estradiol suppresses lipopolysaccharide-induced acute lung injury through PI3K/Akt/SGK1 mediated up-regulation of epithelial sodium channel (ENaC) in vivo and in vitro.
17β-estradiol suppresses lipopolysaccharide-induced acute lung injury through PI3K/Akt/SGK1 mediated up-regulation of epithelial sodium channel (ENaC) in vivo and in vitro.
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17β-雌二醇通过 PI3K/Akt/SGK1 介导的上皮钠通道 (ENaC) 体内和体外上调抑制脂多糖诱导的急性肺损伤
DOI：
10.1186/s12931-014-0159-1
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发表时间：
2014-12-31
影响因子：
5.8
通讯作者：
Feng L
中科院分区：
文献类型：
--
作者：
Qi D;He J;Wang D;Deng W;Zhao Y;Ye Y;Feng L
17β - 雌二醇能够抑制急性肺损伤（ALI）并调节肺泡上皮钠通道（ENaC）。然而，这两种功能之间的关系仍不清楚。本研究旨在评估ENaC以及PI3K/Akt/SGK1信号通路在17β - 雌二醇治疗减轻脂多糖（LPS）诱导的ALI中的作用。
通过气管内给予脂多糖（LPS）在C57BL/J雄性小鼠中诱导ALI。在给予LPS的同时，向ALI模型小鼠给予17β - 雌二醇或无菌生理盐水，同时给予或不给予磷脂酰肌醇3 - 激酶（PI3K）抑制剂渥曼青霉素。在体内LPS刺激4小时后，测量肺组织学变化、支气管肺泡灌洗液（BALF）中的炎症介质、湿/干重比（W/D）以及肺泡液体清除率（AFC）。对于体外研究，在17β - 雌二醇处理之前，将LPS刺激的MLE - 12细胞在有或无渥曼青霉素的情况下预孵育30分钟。通过逆转录酶PCR、蛋白质印迹、细胞表面生物素化和免疫组织化学评估ENaC亚单位的表达。通过蛋白质印迹研究肺组织和肺细胞系中磷酸化Akt和SGK1的水平。
17β - 雌二醇通过减少炎症介质和增强AFC抑制了小鼠中LPS介导的ALI。17β - 雌二醇促进了α - ENaC的表达和表面丰度，并在LPS刺激后提高了磷酸化 - Akt和磷酸化 - SGK1的水平。这种诱导作用在体内和体外均被PI3K抑制剂渥曼青霉素消除。
17β - 雌二醇减轻LPS诱导的ALI不仅通过抑制炎症，还通过提高α - ENaC表达和膜丰度来减轻肺水肿。这些作用至少部分是通过激活PI3K/Akt/SGK1信号通路介导的。
17β-estradiol can suppress acute lung injury (ALI) and regulate alveolar epithelial sodium channel (ENaC). However the relationship between these two functions remains unclear. This study is conducted to assess the role of ENaC and the PI3K/Akt/SGK1 signaling pathway in 17β-estradiol therapy in attenuating LPS-induced ALI. ALI was induced in C57BL/J male mice by intratracheal administration of lipopolysaccharide (LPS). Concurrent with LPS administration, 17β-estradiol or sterile saline was administered to ALI model with or without the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. The lung histological changes, inflammatory mediators in bronchoalveolar lavage fluid (BALF), wet/dry weight ratio (W/D) and alveolar fluid clearance (AFC) were measured 4 hours after LPS challenge in vivo. For in vitro studies, LPS-challenged MLE-12 cells were pre-incubated with or without wortmannin for 30 minutes prior to 17β-estradiol treatment. Expression of ENaC subunits was assessed by reverse transcriptase PCR, western blot, cell surface biotinylation, and immunohistochemistry. The levels of phosphorylated Akt and SGK1 in lung tissue and lung cell lines were investigated by western blot. 17β-estradiol suppressed LPS-mediated ALI in mice by diminishing inflammatory mediators and enhancing AFC. 17β-estradiol promoted the expression and surface abundance of α-ENaC, and increased the levels of phosphorylated-Akt and phosphorylated-SGK1 following LPS challenge. This induction was abolished by the PI3K inhibitor wortmannin in vivo and in vitro. 17β-estradiol attenuates LPS-induced ALI not only by repressing inflammation, but also by reducing pulmonary edema via elevation of α-ENaC expression and membrane abundance. These effects were mediated, at least partially, via activation of the PI3K/Akt/SGK1 signaling pathway.
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影响因子：
5.8
作者：
Deng W;Li CY;Tong J;Zhang W;Wang DX
通讯作者：
Wang DX
影响因子：
3.8
作者：
Hsu, Jun-Te;Kan, Wen-Hong;Chaudry, Irshad H.
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影响因子：
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影响因子：
2.9
作者：
Anadkat, J. S.;Kuzniewicz, M. W.;Chaudhari, B. P.;Cole, F. S.;Hamvas, A.
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Hamvas, A.
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作者：
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Avunduk, MC