Activation of SGK1 in Endometrial Epithelial Cells in Response to PI3K/AKT Inhibition Impairs Embryo Implantation.
Cell Physiol Biochem
; 39(5): 2077-2087, 2016.
Article
em En
| MEDLINE
| ID: mdl-27825168
ABSTRACT
BACKGROUND:
Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation. METHODS/RESULTS:
Here, we report that treatment of endometrial epithelial cells with specific inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT activity pathway results in reciprocal activation of SGK1. Flushing of the uterine lumen of mice with a cell permeable, substrate competitive phosphatidylinositol analogue that inhibits AKT activation (AKT inhibitor III) resulted in Sgk1 phosphorylation, down-regulation of the E3 ubiquitin-protein ligase Nedd4-2, and increased expression of epithelial Na+ channels (ENaC). Furthermore, exposure of the uterine lumen to AKT inhibitor III prior to embryo transfer induced a spectrum of early pregnancy defects, ranging from implantation failure to aberrant spacing of implantation sites.CONCLUSION:
Taken together, our data indicate that the balanced activities of two related serine/threonine kinases, AKT and SGK1, critically govern the implantation process.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Implantação do Embrião
/
Fosfatidilinositóis
/
Proteínas Serina-Treonina Quinases
/
Proteínas Imediatamente Precoces
/
Fosfatidilinositol 3-Quinases
/
Inibidores de Proteínas Quinases
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha