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

Autoři: Davide Marchi aff001;  Kirankumar Santhakumar aff002;  Eleanor Markham aff001;  Nan Li aff003;  Karl-Heinz Storbeck aff004;  Nils Krone aff003;  Vincent T. Cunliffe aff001;  Fredericus J. M. van Eeden aff001
Působiště autorů: The Bateson Centre & Department of Biomedical Science, Firth Court, University of Sheffield, Western Bank, Sheffield, United Kingdom aff001;  Department of Genetic Engineering, SRM Institute of Science and Technology Kattankulathur, India aff002;  The Bateson Centre & Department of Oncology and Metabolism, School of Medicine, University of Sheffield, Sheffield, United Kingdom aff003;  Department of Biochemistry, Stellenbosch University, Stellenbosch, Matieland, South Africa aff004;  Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany aff005
Vyšlo v časopise: Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008757
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008757


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.

Klíčová slova:

Cellular crosstalk – Cortisol – Embryos – Gene expression – Larvae – Medical hypoxia – Tails – Zebrafish


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