Open Access

Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide‑induced lung injury

  • Authors:
    • Wang Deng
    • Chang‑Yi Li
    • Jin Tong
    • Jing He
    • Yan Zhao
    • Dao‑Xin Wang
  • View Affiliations

  • Published online on: January 2, 2019     https://doi.org/10.3892/mmr.2019.9809
  • Pages: 1665-1677
  • Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial sodium channel (ENaC) provides the driving force for the removal of edema from the alveolar spaces in acute lung injury (ALI). Our previous study reported that insulin increased the expression of α‑ENaC, possibly via the serum/glucocorticoid‑inducible kinase‑1 (SGK1) pathway in ALI; however, the upstream regulator of SGK1 activity remains unclear. In the current study, C3H/HeN mice were subjected to lipopolysaccharide (LPS)‑induced lung injury without hyperglycemia. Exogenous insulin was administered intravenously using a micro‑osmotic pump, and intratracheal delivery of SGK1 small interfering RNA (siRNA) was performed. Furthermore, alveolar epithelial type II cells transfected with phosphatidylinositol 3‑kinase (PI3K) siRNA or SGK1 siRNA were incubated with insulin. Insulin protected the pulmonary epithelial barrier, reduced the apoptosis of alveolar epithelial cells, attenuated pulmonary edema, improved alveolar fluid clearance, and increased the expression levels of α‑, β‑ and γ‑ENaC in mice. In addition, in alveolar epithelial cells, insulin increased the expression levels of α‑, β‑ and γ‑ENaC, as well as the level of phosphorylated SGK1, which were then inhibited by the selective targeting of PI3K or SGK1 by siRNA. Taken together, the results of the present study demonstrated that insulin protected the lung epithelium and attenuated pulmonary edema through the upregulation of ENaC via the PI3K/SGK1 pathway in LPS‑induced lung injury.
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March-2019
Volume 19 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Deng W, Li CY, Tong J, He J, Zhao Y and Wang DX: Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide‑induced lung injury. Mol Med Rep 19: 1665-1677, 2019.
APA
Deng, W., Li, C., Tong, J., He, J., Zhao, Y., & Wang, D. (2019). Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide‑induced lung injury. Molecular Medicine Reports, 19, 1665-1677. https://doi.org/10.3892/mmr.2019.9809
MLA
Deng, W., Li, C., Tong, J., He, J., Zhao, Y., Wang, D."Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide‑induced lung injury". Molecular Medicine Reports 19.3 (2019): 1665-1677.
Chicago
Deng, W., Li, C., Tong, J., He, J., Zhao, Y., Wang, D."Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharide‑induced lung injury". Molecular Medicine Reports 19, no. 3 (2019): 1665-1677. https://doi.org/10.3892/mmr.2019.9809