کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10903940 | 1086541 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Insulin upregulates the expression of epithelial sodium channel in vitro and in a mouse model of acute lung injury: Role of mTORC2/SGK1 pathway
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
PIP3PI3KLPSAT IIPDK1SGK1AFCmTORC2mTORC1Nedd4-2ARDSAGCENaC - ENACAcute lung injury - آسیب ریه حادAkt - آکتAli - اماinsulin - انسولینalveolar fluid clearance - ترخیص مایعات آلوئولارAcute respiratory distress syndrome - سندرم دیسترس تنفسی حادPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازphosphatidylinositol 3,4,5-trisphosphate - فسفاتیدیلینواستیل 3،4،5-تری فسفاتlipopolysaccharide - لیپوپلی ساکاریدMammalian target of rapamycin complex 2 - هدف پستانداران رپامایسین 2Mammalian target of rapamycin complex - هدف پستانداران مجتمع رپامایسینMammalian target of rapamycin complex 1 - هدف پستانداران مجتمع رپامایسین 1protein kinase B - پروتئین کیناز Bepithelial sodium channel - کانال سدیم اپیتلیالphosphoinositide-dependent kinase - کیناز وابسته به فسفوئینوزیته
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by proteinaceous pulmonary edema and severe arterial hypoxemia with a mortality of approximately 40%. Stimulation of epithelial sodium channel (ENaC) promotes Na+ transport, a rate-limiting step for pulmonary edema reabsorption. Insulin is known to participate in the ion transport; however, its role in pulmonary edema clearance and the regulatory mechanism involved have not been fully elucidated. In the current study, in a lipopolysaccharide-based mouse model of ALI, we found that insulin alleviated pulmonary edema by promoting ENaC-mediated alveolar fluid clearance through serum and glucocorticoid induced kinase-1 (SGK1). In alveolar epithelial cells, insulin increased the expression of α-, β-, and γ-ENaC, which was blocked by the mammalian target of rapamycin complex 2 (mTORC2) inhibitor or knockdown of Rictor (a necessary component of mTORC2), and SGK1 inhibitor, respectively. In addition, an immunoprecipitation study demonstrated that SGK1(Ser422) phosphorylation, the key step for complete SGK1 activation by insulin, was conducted through PI3K/mTORC2 pathway. Finally, we testified the role of mTORC2 in vivo by demonstrating that PP242 prevented insulin-stimulated SGK1 activation and ENaC increase during ALI. The data revealed that during ALI, insulin stimulates alveolar fluid clearance by upregulating the expression of α-, β-, and γ-ENaC at the cell surface, which was, at least, partially through activating mTROC2/SGK1 signaling pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 331, Issue 1, 1 February 2015, Pages 164-175
Journal: Experimental Cell Research - Volume 331, Issue 1, 1 February 2015, Pages 164-175
نویسندگان
Jing He, Di Qi, Dao-xin Wang, Wang Deng, Yuan Ye, Long-hua Feng, Tao Zhu, Yan Zhao, Chun-rong Zhang,