Studies of genetic iron overload and deficiency in mice and humans have identified the hormonal hepcidin/ferroportin system as the key regulator of systemic iron fluxes. Hepcidin is a hepatic peptide hormone that is controlled by iron availability, erythropoietic activity and inflammation. It binds to the iron export channel ferroportin located especially on the surface of macrophages, hepatocytes and intestinal enterocytes to cause its internalization and proteolysis. In accordance with this mechanism chronically elevated hepcidin levels (e.g. in the anemia of chronic diseases; ACD) cause systemic iron deficiency and inappropriately low hepcidin levels (e.g. in hereditary hemochromatosis; HH) result in iron overload.
The aim of our research is to identify genes and cellular processes that control hepcidin-mediated Fpn expression. To achieve this goal we apply genome-wide siRNA knock down using RNAi arrays, a novel and highly innovative technology established within the MMPU (Rainer Pepperkok). We expect to discover target genes (e.g. kinases) suitable for pharmacological manipulation establishing the basis for novel treatment options of iron-related disorders.