Class 3 phosphoinositide 3-kinase promotes hepatic glucocorticoid receptor stability and transcriptional activity.

ABSTRACT:

Aim

Lipid kinase class 3 phosphoinositide 3-kinase (PI3K) and nuclear receptor transcription factor glucocorticoid receptor (GR) play essential physiological roles in metabolic adaptation to fasting by activating lysosomal degradation by autophagy and metabolic gene expression, yet their functional interaction is unknown. The requirement of class 3 PI3K for GR function was investigated in liver tissue.

Methods

Inactivation of class 3 PI3K was achieved through deletion of its essential regulatory subunit Vps15, by expressing Cre-recombinase in the livers of Vps15^f/f mice. The response to both 24-h fasting and synthetic GR ligand, dexamethasone (DEX) was evaluated in control and mutant mice. Liver tissue was analysed by immunoblot, RT-qPCR, and LC-MS.

Results

SUBMITTER: Shibayama Y 

PROVIDER: S-EPMC9539506 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature