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Reprogramming of glucocorticoid receptor function by hypoxia

Tineke Vanderhaeghen (UGent) , Steven Timmermans (UGent) , Deepika Watts, Ville Paakinaho, Melanie Eggermont (UGent) , Jolien Vandewalle (UGent) , Charlotte Wallaeys (UGent) , Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens (UGent) , et al.
(2022) EMBO REPORTS. 23(1).
Author
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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 HIF1 alpha and HIF2 alpha 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.
Keywords
FATTY-ACID OXIDATION, CORTICOSTERONE RESPONSE, LIPID-ACCUMULATION, FASTING RESPONSE, DNA-BINDING, PPAR-ALPHA, GENE, INDUCTION, OXYGEN, LIVER, crosstalk, hypoxia, inflammation, mechanism, metabolism

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Citation

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MLA
Vanderhaeghen, Tineke, et al. “Reprogramming of Glucocorticoid Receptor Function by Hypoxia.” EMBO REPORTS, vol. 23, no. 1, 2022, doi:10.15252/embr.202153083.
APA
Vanderhaeghen, T., Timmermans, S., Watts, D., Paakinaho, V., Eggermont, M., Vandewalle, J., … Libert, C. (2022). Reprogramming of glucocorticoid receptor function by hypoxia. EMBO REPORTS, 23(1). https://doi.org/10.15252/embr.202153083
Chicago author-date
Vanderhaeghen, Tineke, Steven Timmermans, Deepika Watts, Ville Paakinaho, Melanie Eggermont, Jolien Vandewalle, Charlotte Wallaeys, et al. 2022. “Reprogramming of Glucocorticoid Receptor Function by Hypoxia.” EMBO REPORTS 23 (1). https://doi.org/10.15252/embr.202153083.
Chicago author-date (all authors)
Vanderhaeghen, Tineke, Steven Timmermans, Deepika Watts, Ville Paakinaho, Melanie Eggermont, Jolien Vandewalle, Charlotte Wallaeys, Lise Van Wyngene, Kelly Van Looveren, Louise Nuyttens, Sylviane Dewaele, Joke Vanden Berghe, Kelly Lemeire, Joey De Backer, Laura Dirkx, Wim Vanden Berghe, Guy Caljon, Bart Ghesquiere, Karolien De Bosscher, Ben Wielockx, Jorma J. Palvimo, Rudi Beyaert, and Claude Libert. 2022. “Reprogramming of Glucocorticoid Receptor Function by Hypoxia.” EMBO REPORTS 23 (1). doi:10.15252/embr.202153083.
Vancouver
1.
Vanderhaeghen T, Timmermans S, Watts D, Paakinaho V, Eggermont M, Vandewalle J, et al. Reprogramming of glucocorticoid receptor function by hypoxia. EMBO REPORTS. 2022;23(1).
IEEE
[1]
T. Vanderhaeghen et al., “Reprogramming of glucocorticoid receptor function by hypoxia,” EMBO REPORTS, vol. 23, no. 1, 2022.
@article{8730033,
  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 HIF1 alpha and HIF2 alpha 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.}},
  articleno    = {{e53083}},
  author       = {{Vanderhaeghen, Tineke and Timmermans, Steven and Watts, Deepika and Paakinaho, Ville and Eggermont, Melanie and Vandewalle, Jolien and Wallaeys, Charlotte and Van Wyngene, Lise and Van Looveren, Kelly and Nuyttens, Louise and Dewaele, Sylviane and Vanden Berghe, Joke and Lemeire, Kelly and De Backer, Joey and Dirkx, Laura and Vanden Berghe, Wim and Caljon, Guy and Ghesquiere, Bart and De Bosscher, Karolien and Wielockx, Ben and Palvimo, Jorma J. and Beyaert, Rudi and Libert, Claude}},
  issn         = {{1469-221X}},
  journal      = {{EMBO REPORTS}},
  keywords     = {{FATTY-ACID OXIDATION,CORTICOSTERONE RESPONSE,LIPID-ACCUMULATION,FASTING RESPONSE,DNA-BINDING,PPAR-ALPHA,GENE,INDUCTION,OXYGEN,LIVER,crosstalk,hypoxia,inflammation,mechanism,metabolism}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{26}},
  title        = {{Reprogramming of glucocorticoid receptor function by hypoxia}},
  url          = {{http://dx.doi.org/10.15252/embr.202153083}},
  volume       = {{23}},
  year         = {{2022}},
}
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