CORDIS - EU research results

HIF and hepcidin : missing links between infection, iron metabolism and cancer ?

Final Report Summary - HIFHEPC (HIF and hepcidin : missing links between infection, iron metabolism and cancer ?)

Hepcidin is the key iron regulatory hormone capable of blocking iron absorption from the duodenum and iron release from macrophages. Mutations affecting hepcidin regulators or the hepcidin gene itself cause hemochromatosis, a common genetic disorder, characterized by iron overload in various tissues.
Current treatments for iron overload disorders (such as hemochromatosis) are limited to phlebotomy or, in case of severe anemia, cardiac failure, or poor tolerance, to chelation therapies. We showed that deleting the Hypoxia-Inducible transcription factor HIF-2 in the intestine prevented iron overload in a murine model of hemochromatosis. Therefore, therapeutic intervention on intestinal HIF-2 activity might be beneficial to reduce the rates of iron absorption and parenchymal iron overload.
We also showed that stabilization of hepatic HIF-2 down-regulates hepcidin expression through increased erythropoiesis and erythropoietin production. Therefore, the ability of hepatic HIF-2 to repress hepcidin in order to increase iron absorption may be clinically interesting in the treatment of patients with chronic kidney disease, resulting in renal anemia.
Finally, while hepcidin is known as the key iron regulatory hormone, we identified a completely new role of this peptide as a major component of innate immunity. Hepcidin may constitute a potential new target for acute, chronic inflammation but also systemic inflammation.