Reprogramming of glucocorticoid receptor function by hypoxia

ABSTRACT: Here, we investigate the impact of hypoxia on the hepatic response of glucocorticoid receptor (GR) to dexamethasone (DEX) in mice via RNA-sequencing. Hypoxia causes three types of reprogramming of GR: (i) much weaker induction of classical GR response genes by DEX in hypoxia (ii) a number of genes is induced by DEX specifically in hypoxia and (iii) hypoxia induces a group of genes via activation of the hypothalamic-pituitary-adrenal (HPA) axis. Transcriptional profiles are reflected by changed GR-DNA binding as measured by ChIP sequencing. The HPA axis is induced by hypothalamic HIF1α and HIF2α activation and leads to GR-dependent lipolysis and ketogenesis. Acute inflammation, induced by lipopolysaccharide, is prevented by DEX in normoxia but not during hypoxia, and this is attributed to H

SUBMITTER: Ms. Tineke Vanderhaeghen 

PROVIDER: S-SCDT-EMBOR-2021-53083-T | biostudies-other |

REPOSITORIES: biostudies-other