PUBLICATION
Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae
- Authors
- Marchi, D., Santhakumar, K., Markham, E., Li, N., Storbeck, K.H., Krone, N., Cunliffe, V.T., van Eeden, F.J.M.
- ID
- ZDB-PUB-200508-9
- Date
- 2020
- Source
- PLoS Genetics 16: e1008757 (Journal)
- Registered Authors
- Cunliffe, Vincent, Marchi, Davide, Markham, Elenor R., Santhakumar, Kiran, van Eeden, Freek
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Aryl Hydrocarbon Receptor Nuclear Translocator/genetics
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/genetics
- Glucocorticoids/metabolism
- Glucocorticoids/pharmacology*
- Hypoxia-Inducible Factor 1/metabolism
- Hypoxia-Inducible Factor 1/physiology*
- Larva/genetics
- Larva/metabolism
- Receptor Cross-Talk/drug effects
- Receptor Cross-Talk/physiology*
- Receptors, Glucocorticoid/metabolism
- Receptors, Glucocorticoid/physiology
- Signal Transduction/drug effects
- Signal Transduction/genetics
- Tumor Suppressor Proteins/genetics
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/growth & development
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- PubMed
- 32379754 Full text @ PLoS Genet.
Citation
Marchi, D., Santhakumar, K., Markham, E., Li, N., Storbeck, K.H., Krone, N., Cunliffe, V.T., van Eeden, F.J.M. (2020) Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae. PLoS Genetics. 16:e1008757.
Abstract
In the last decades in vitro studies highlighted the potential for crosstalk between Hypoxia-Inducible Factor-(HIF) and glucocorticoid-(GC) signalling pathways. However, how this interplay precisely occurs in vivo is still debated. Here, we use zebrafish larvae (Danio rerio) to elucidate how and to what degree hypoxic signalling affects the endogenous glucocorticoid pathway and vice versa, in vivo. Firstly, our results demonstrate that in the presence of upregulated HIF signalling, both glucocorticoid receptor (Gr) responsiveness and endogenous cortisol levels are repressed in 5 days post fertilisation larvae. In addition, despite HIF activity being low at normoxia, our data show that it already impedes both glucocorticoid activity and levels. Secondly, we further analysed the in vivo contribution of glucocorticoids to HIF activity. Interestingly, our results show that both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play a key role in enhancing it. Finally, we found indications that glucocorticoids promote HIF signalling via multiple routes. Cumulatively, our findings allowed us to suggest a model for how this crosstalk occurs in vivo.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping