| Literature DB >> 34699114 |
Tineke Vanderhaeghen1,2, Steven Timmermans1,2, Deepika Watts3,4, Ville Paakinaho5, Melanie Eggermont1,2, Jolien Vandewalle1,2, Charlotte Wallaeys1,2, Lise Van Wyngene1,2, Kelly Van Looveren1,2, Louise Nuyttens1,2, Sylviane Dewaele1,2, Joke Vanden Berghe1,2, Kelly Lemeire1,2, Joey De Backer6, Laura Dirkx6, Wim Vanden Berghe6, Guy Caljon6, Bart Ghesquière7,8, Karolien De Bosscher9,10, Ben Wielockx3,4, Jorma J Palvimo5, Rudi Beyaert1,2, Claude Libert1,2.
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-responsive 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 HPA axis activation by hypoxia. We unfold new physiological pathways that have consequences for patients suffering from GC resistance.Entities:
Keywords: crosstalk; hypoxia; inflammation; mechanism; metabolism
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Year: 2021 PMID： 34699114 PMCID： PMC8728616 DOI： 10.15252/embr.202153083
Source DB: PubMed Journal: EMBO Rep ISSN： 1469-221X Impact factor: 8.807