Journal of Jilin University Medicine Edition ›› 2015, Vol. 41 ›› Issue (04): 716-720.doi: 10.13481/j.1671-587x.20150409

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Mechanism of insulin in up-regulating epithelial sodium channel α-subunit via mTORC2/SGK1 signaling pathway

HE Jing, QI Di, WANG Daoxin   

  1. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
  • Received:2014-10-20 Published:2015-08-01

Abstract:

Objective To study the role of mTORC2/SGK1 signaling pathway in the up-regulation of alveolar epithelial sodium channel α-subunit (α-ENaC) by insulin,and to clarify the mechanism of insulin in promoting the lung edema clearance in the acute lung injury(ALI) mice. Methods The C57BL/6J mice were randomly divided into control group,LPS group,insulin group (LPS+insulin),PP242 group (PP242+LPS+insulin) and rapamycin group (rapamycin+LPS+insulin),with 10 mice in each group. The lung wet/dry weight(W/D) ratios and alveolar fluid clearance(AFC) of the mice were detected. HE staining was used to observe the pathological changes of lung tissue. The protein expression levels of α-ENaC and phosphorylated serum-and the levels of glucocorticoid-inducible kinase 1 (SGK1) at Ser422 in lung tissue were determined by Western blotting method. Results Compared with LPS group, the lung injury score and W/D ratio in insulin group were decreased significantly (P<0.05) and the AFC was increased significantly (P<0.05).The expression level of α-ENaC protein in LPS group was decreased significantly compared with control group (P<0.05). The expression levels of both α-ENaC protein and pSGK1(Ser422) in insulin group were significantly increased compared with LPS group (P<0.05).Compared with insulin group,the α-ENaC protein expression level and phosphorylated SGK1(Ser422) levelin PP242 group were decreased(P<0.05). Conclusion Through mTORC2 pathway,insulin activates the SGK1 and up-regulates the expression of α-ENaC protein to accelerate the AFC,which is beneficial to the prognosis of ALI/acute respiratory distress syndrome(ARDS).

Key words: acute lung injury, acute respiratory distress syndrome, insulin, serum-and glucocorticoid-inducible kinase 1, epithelial sodium channel, mammalian target of rapamycin complex

CLC Number: 

  • R563.8