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Vanderhaeghen T, Timmermans S, Watts D, et al. Reprogramming of glucocorticoid receptor function by hypoxia. EMBO Rep. 2021;23(1):e53083doi: 10.15252/embr.202153083.
Vanderhaeghen, T., Timmermans, S., Watts, D., Paakinaho, V., Eggermont, M., Vandewalle, J., Wallaeys, C., Van Wyngene, L., Van Looveren, K., Nuyttens, L., Dewaele, S., Vanden Berghe, J., Lemeire, K., De Backer, J., Dirkx, L., Vanden Berghe, W., Caljon, G., Ghesquière, B., De Bosscher, K., Wielockx, B., Palvimo, J. J., Beyaert, R., & Libert, C. (2022). Reprogramming of glucocorticoid receptor function by hypoxia. EMBO reports, 23(1), e53083. https://doi.org/10.15252/embr.202153083
Vanderhaeghen, Tineke, et al. "Reprogramming of glucocorticoid receptor function by hypoxia." EMBO reports vol. 23,1 (2022): e53083. doi: https://doi.org/10.15252/embr.202153083
Vanderhaeghen T, Timmermans S, Watts D, Paakinaho V, Eggermont M, Vandewalle J, Wallaeys C, Van Wyngene L, Van Looveren K, Nuyttens L, Dewaele S, Vanden Berghe J, Lemeire K, De Backer J, Dirkx L, Vanden Berghe W, Caljon G, Ghesquière B, De Bosscher K, Wielockx B, Palvimo JJ, Beyaert R, Libert C. Reprogramming of glucocorticoid receptor function by hypoxia. EMBO Rep. 2022 Jan 05;23(1):e53083. doi: 10.15252/embr.202153083. Epub 2021 Oct 26. PMID: 34699114; PMCID: PMC8728616.
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EMBO Rep. 2022 Jan 05;23(1):e53083. doi: 10.15252/embr.202153083. Epub 2021 Oct 26.

Reprogramming of glucocorticoid receptor function by hypoxia.

EMBO reports

Tineke Vanderhaeghen, 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 Ghesquière, Karolien De Bosscher, Ben Wielockx, Jorma J Palvimo, Rudi Beyaert, Claude Libert

Affiliations

  1. VIB Center for Inflammation Research, Ghent, Belgium.
  2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  3. Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
  4. DFG Research Centre and Cluster of Excellence for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
  5. Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
  6. Department of Biomedical Sciences, University of Antwerp, Universiteitsplein, Wilrijk, Belgium.
  7. Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium.
  8. Metabolomics Expertise Center, Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium.
  9. Translational Nuclear Receptor Research Lab, VIB Center for Medical Biotechnology, Ghent, Belgium.
  10. Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

PMID: 34699114 PMCID: PMC8728616 DOI: 10.15252/embr.202153083

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.

© 2021 The Authors.

Keywords: crosstalk; hypoxia; inflammation; mechanism; metabolism

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