In 2001, we described for the first time the critical and irreplaceable role of hepcidin in the regulation of iron homeostasis. At that time, we made the pioneer demonstration that hepcidin is an hyposideremic hormone acting to repress the iron availability into the body (read this comment). We also made the demonstration that hepcidin expression is regulated by anemia, hypoxia and more importantly by inflammation. By developing a turpentine abcess-induced inflammation in hepcidin-deficient mice we are the first to unambiguously demonstrate the crucial role of hepcidin in the dysregulation of iron homeostasis during inflammation. We were the first to describe that erythropoietin injection completely turns off hepcidin expression, a mechanism required to allow strong iron avaibility for production of new red blood cells. This protocol based on erythropoietin injection could be used to discover new proteins involved in the downregulation of hepcidin expression. Finally, we demonstrated that hemochromatosis is an hepatic metabolic disease due an insufficient production of hepcidin. We made the proof-of-principle that restoring a normal or higher production of hepcidin completely protects the organism against iron overload.
MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype