Insulin ameliorates pulmonary edema through the upregulation of epithelial sodium channel via the PI3K/SGK1 pathway in mice with lipopolysaccharideinduced lung injury.
Mol Med Rep
; 19(3): 1665-1677, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-30628684
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 αENaC, possibly via the serum/glucocorticoidinducible kinase1 (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 microosmotic pump, and intratracheal delivery of SGK1 small interfering RNA (siRNA) was performed. Furthermore, alveolar epithelial type II cells transfected with phosphatidylinositol 3kinase (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, ß and γENaC in mice. In addition, in alveolar epithelial cells, insulin increased the expression levels of α, ß and γENaC, 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 LPSinduced lung injury.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Edema Pulmonar
/
Proteínas Serina-Treonina Quinases
/
Proteínas Imediatamente Precoces
/
Canais Epiteliais de Sódio
/
Lesão Pulmonar
/
Insulina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2019
Tipo de documento:
Article