Marchi, D. orcid.org/0000-0002-0991-1738, Santhakumar, K., Markham, E. et al. (5 more authors) (2020) Bidirectional crosstalk between hypoxia-inducible factor and glucocorticoid signalling in zebrafish larvae. PLOS Genetics, 16 (5). e1008757. ISSN 1553-7390
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.
Metadata
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Copyright, Publisher and Additional Information: | © 2020 The Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||||||
Dates: |
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Institution: | The University of Sheffield | ||||||
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) | ||||||
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Depositing User: | Symplectic Sheffield | ||||||
Date Deposited: | 18 May 2020 08:24 | ||||||
Last Modified: | 18 May 2020 08:24 | ||||||
Status: | Published online | ||||||
Publisher: | Public Library of Science (PLoS) | ||||||
Refereed: | Yes | ||||||
Identification Number: | https://doi.org/10.1371/journal.pgen.1008757 |