Reprogramming of glucocorticoid receptor function by hypoxia
© 2021 The Authors..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
EMBO reports - 23(2022), 1 vom: 05. Jan., Seite e53083 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vanderhaeghen, Tineke [VerfasserIn] |
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| Links: |
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| Themen: |
7S5I7G3JQL |
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| Anmerkungen: |
Date Completed 14.03.2022 Date Revised 02.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.202153083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332391671 |
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| 245 | 1 | 0 | |a Reprogramming of glucocorticoid receptor function by hypoxia |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a hypoxia | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a mechanism | |
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| 700 | 1 | |a Paakinaho, Ville |e verfasserin |4 aut | |
| 700 | 1 | |a Eggermont, Melanie |e verfasserin |4 aut | |
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