Document Detail


Insulin Upregulates the expression of epithelial sodium channel in vitro and in a mouse model of acute lung injury: Role of mTORC2/SGK1 pathway.
MedLine Citation:
PMID:  25265063     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Jing He; Di Qi; Dao-Xin Wang; Wang Deng; Yuan Ye; Long-Hua Feng; Tao Zhu; Yan Zhao; Chun-Rong Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-26
Journal Detail:
Title:  Experimental cell research     Volume:  -     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-29     Completed Date:  -     Revised Date:  2014-9-30    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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