HIF-GC crosstalk-DM Poster.pdf

Hypoxia is a pathophysiological condition to which cells rapidly respond via the activity of Hypoxia-Inducible Factors (HIFs) in order to restore homeostasis and to prevent metabolic shutdown. It can be maladaptive and contributes to inflammation, tissue ischemia, stroke and growth of solid tumours. Synthetic glucocorticoids (GC) have been used for decades as anti-inflammatory drugs for treating pathological conditions linked to hypoxia.

In vitro studies highlighted the presence of a crosstalk between HIF and GC. However, how it occurs in vivo and what the molecular mechanism is behind it are questions that still remain unanswered. We are using zebrafish larvae characterized by the presence of hypoxia reporter line Tg(phd3:eGFP) to elucidate how and to what degree HIF signalling affects the endogenous GC pathway and vice versa. Indeed, zebrafish cellular processes, genetic pathways and organs are highly conserved with other vertebrates.

Using a combination of hypoxia reporter, targeted mutagenesis, transcriptomics, pharmacological and in vivo imaging analysis, we provide a logical model of interaction between HIF and GC signalling. Our results are important because they suggest a novel route to efficiently downregulate HIF for clinical purposes.