Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae

Marchi, Davide; Santhakumar, Kirankumar; Markham, Eleanor; Li, Nan; Storbeck, Karl-Heinz; Krone, Nils; Cunliffe, Vincent T.; Eeden, Fredericus J.M. van

doi:10.1371/journal.pgen.1008757

Cited by 32 publications

(22 citation statements)

References 84 publications

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“…Many other pathways were impacted by VitE deficiency, of note is collagen remodeling. egln3 , expressed in the neural plate in 12 hpf zebrafish embryos [ 32 ], is a hypoxia inducible factor (HIF) target and regulates the expression of collagen remodeling genes p4ha1b , plod1a and col1a1b [ 49 , 50 ]. VitE radicals produced as a result of lipid peroxidation reactions are chemically reduced by ascorbic acid (Vitamin C (VitC)), thereby depleting this critical antioxidant micronutrient [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

et al. 2021

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Vitamin E (VitE) is essential for vertebrate embryogenesis, but the mechanisms involved remain unknown. To study embryonic development, we fed zebrafish adults (>55 days) either VitE sufficient (E+) or deficient (E–) diets for >80 days, then the fish were spawned to generate E+ and E– embryos. To evaluate the transcriptional basis of the metabolic and phenotypic outcomes, E+ and E– embryos at 12, 18 and 24 h post-fertilization (hpf) were subjected to gene expression profiling by RNASeq. Hierarchical clustering, over-representation analyses and gene set enrichment analyses were performed with differentially expressed genes. E– embryos experienced overall disruption to gene expression associated with gene transcription, carbohydrate and energy metabolism, intracellular signaling and the formation of embryonic structures. mTOR was apparently a major controller of these changes. Thus, embryonic VitE deficiency results in genetic and transcriptional dysregulation as early as 12 hpf, leading to metabolic dysfunction and ultimately lethal outcomes.

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Section: Discussionmentioning

confidence: 99%

Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

et al. 2021

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“…These results are confirmed by Marchi et al They have also demonstrated the repression of GR activity and its reduced responsiveness to exogenous GCs when HIF protein levels are upregulated in vhl -/zebrafish. Furthermore, cortisol levels were also reduced suggesting that HIF signalling can act both at the level of the hypothalamus by inhibiting Pomc expression and intracellularly by blocking the transcriptional activity of GR itself (82). A recent…”

Section: The In Vivo Crosstalk Between Hif and Gr And Its Role In Inflammationmentioning

confidence: 98%

“…GCs stabilize HIF via pVHL degradation HIF represses GR activity and the GR response to exogenous GCs (e.g. BME) in vhl -/zebrafish larvae (81,82) Cortisol levels are reduced by HIF due to repression of POMC expression and intracellular blocking the transcriptional activity of GR GCs in AMS Prophylactic effect of GCs when ascending to high altitude Administration of GCs (DEX and prednisolone) prior to ascending to high altitude reduces the symptoms of AMS (suppresses inflammatory pathways, reduces vascular permeability and vasoconstriction, improves arterial oxygenation and induces a better antioxidant-oxidant balance) (83-88)…”

Section: In Vivomentioning

confidence: 99%

Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease

2021

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Glucocorticoid-induced (GC) and hypoxia-induced transcriptional responses play an important role in tissue homeostasis and in the regulation of cellular responses to stress and inflammation. Evidence exists that there is an important crosstalk between both GC and hypoxia effects. Hypoxia is a pathophysiological condition to which cells respond quickly in order to prevent metabolic shutdown and death. The hypoxia inducible factors (HIFs) are the master regulators of oxygen homeostasis and are responsible for the ability of cells to cope with low oxygen levels. Maladaptive responses of HIFs contribute to a variety of pathological conditions including acute mountain sickness (AMS), inflammation and neonatal hypoxia-induced brain injury. Synthetic GCs which are analogous to the naturally occurring steroid hormones (cortisol in humans, corticosterone in rodents), have been used for decades as anti-inflammatory drugs for treating pathological conditions which are linked to hypoxia (i.e. asthma, ischemic injury). In this review, we investigate the crosstalk between the glucocorticoid receptor (GR), and HIFs. We discuss possible mechanisms by which GR and HIF influence one another, in vitro and in vivo, and the therapeutic effects of GCs on HIF-mediated diseases.

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“…High levels of hypoxia and HIF‐1α are associated with many of these conditions, including asthma, COPD, rheumatoid arthritis (RA), colitis and atherosclerosis [31–34]. Furthermore, HIF signalling interplays with key inflammatory signalling pathways, including glucocorticoids, mTOR and arachidonic acid [35–37].…”

Section: Dampening Hif In Chronic Inflammationmentioning

confidence: 99%

If it’s not one thing, HIF’s another: immunoregulation by hypoxia inducible factors in disease

2020

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Hypoxia‐inducible factors (HIFs) have emerged in recent years as critical regulators of immunity. Localised, low oxygen tension is a hallmark of inflamed and infected tissues. Subsequent myeloid cell HIF stabilisation plays key roles in the innate immune response, alongside emerging oxygen‐independent roles. Manipulation of regulatory proteins of the HIF transcription factor family can profoundly influence inflammatory profiles, innate immune cell function and pathogen clearance and, as such, has been proposed as a therapeutic strategy against inflammatory diseases. The direction and mode of HIF manipulation as a therapy are dictated by the inflammatory properties of the disease in question, with innate immune cell HIF reduction being, in general, advantageous during chronic inflammatory conditions, while upregulation of HIF is beneficial during infections. The therapeutic potential of targeting myeloid HIFs, both genetically and pharmacologically, has been recently illuminated in vitro and in vivo, with an emerging range of inhibitory and activating strategies becoming available. This review focuses on cutting edge findings that uncover the roles of myeloid cell HIF signalling on immunoregulation in the contexts of inflammation and infection and explores future directions of potential therapeutic strategies.

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Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae

Cited by 32 publications

References 84 publications

Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease

If it’s not one thing, HIF’s another: immunoregulation by hypoxia inducible factors in disease

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