Reprogramming of glucocorticoid receptor function by hypoxia

被引：11

作者：

Vanderhaeghen, Tineke ^{[1
,2
]}

Timmermans, Steven ^{[1
,2
]}

Watts, Deepika ^{[3
,4
,5
]}

Paakinaho, Ville ^{[6
]}

Eggermont, Melanie ^{[1
,2
]}

Vandewalle, Jolien ^{[1
,2
]}

Wallaeys, Charlotte ^{[1
,2
]}

Van Wyngene, Lise ^{[1
,2
]}

Van Looveren, Kelly ^{[1
,2
]}

Nuyttens, Louise ^{[1
,2
]}

Dewaele, Sylviane ^{[1
,2
]}

Vanden Berghe, Joke ^{[1
,2
]}

Lemeire, Kelly ^{[1
,2
]}

De Backer, Joey ^{[7
]}

Dirkx, Laura ^{[7
]}

Vanden Berghe, Wim ^{[7
]}

Caljon, Guy ^{[7
]}

Ghesquiere, Bart ^{[8
,9
]}

De Bosscher, Karolien ^{[10
,11
]}

Wielockx, Ben ^{[3
,4
,5
]}

Palvimo, Jorma J. ^{[6
]}

Beyaert, Rudi ^{[1
,2
]}

Libert, Claude ^{[1
,2
]}

机构：

[1] VIB Ctr Inflammat Res, Ghent, Belgium

[2] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium

[3] Tech Univ Dresden, Inst Clin Chem & Lab Med, Dept Clin Pathobiochem, Dresden, Germany

[4] Tech Univ Dresden, DFG Res Ctr, Dresden, Germany

[5] Tech Univ Dresden, Cluster Excellence Regenerat Therapies Dresden, Dresden, Germany

[6] Univ Eastern Finland, Inst Biomed, Kuopio, Finland

[7] Univ Antwerp, Dept Biomed Sci, Univ Pl, Antwerp, Belgium

[8] VIB Ctr Canc Biol, Ctr Canc Biol, Metabol Expertise Ctr, Leuven, Belgium

[9] Katholieke Univ Leuven, Metabol Expertise Ctr, Dept Oncol, Leuven, Belgium

[10] VIB Ctr Med Biotechnol, Translat Nucl Receptor Res Lab, Ghent, Belgium

[11] Univ Ghent, Dept Biomol Med, Ghent, Belgium

来源：

EMBO REPORTS | 2022年 / 23卷 / 01期

关键词：

crosstalk; hypoxia; inflammation; mechanism; metabolism; FATTY-ACID OXIDATION; CORTICOSTERONE RESPONSE; LIPID-ACCUMULATION; FASTING RESPONSE; DNA-BINDING; PPAR-ALPHA; GENE; INDUCTION; OXYGEN; LIVER;

D O I：

10.15252/embr.202153083

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：26

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