Iron is one of the important trace elements for the body as it not only is a component of many biomolecules including haemoglobin but also plays several roles in fundamental biochemical reactions. The lack of iron could therefore result in cellular dysfunction and iron deficiency anaemia. However, iron also involves in the generation of reactive oxygen species. As a result, the presence of excessive iron in the body can result in oxidative stress. Therefore, the balance of iron in the body, or iron homeostasis, is controlled through several regulatory mechanisms at both cellular and systemic levels. Circulatory iron is acquired from

a) reticuloendothelial cells in the spleen, bone marrow, and liver through the reutilisation of iron from senescent erythrocytes and b), to a lesser extent, intestinal absorption from the diet.

Iron is effluxed from enterocytes and reticuloendothelial cells into the circulation through iron exporter protein, ferroportin. Hepcidin, a liver-secreted antimicrobial peptide, plays acentral role in the control of systemic iron homeostasis by inhibiting iron absorption and reticuloendothelial iron recycling. The mechanism of hepcidin-mediated iron homeostasis control is by binding to ferroportin and inducing its internalisation and degradation. Hepatic hepcidin expression is regulated by several stimuli including body iron status, erythropoietic activity, hypoxia and inflammation. Disturbances of systemic iron hemeostatic control can lead to the alteration of body iron status. Disruption of iron sensing pathway and/or hepcidin results in hereditary haemochromatosis, a genetic iron overload disorder. On the contrary, hepcidin induction by chronic inflammatory conditions can play a role in the pathogenesis of anaemia of chronic disease or anaemia of inflammation. Although the mechanisms of hepcidin regulation have been widely studied and reported, the control of hepcidin by erythroietic activity as well as ineffective erythropoiesis have not yet clearly elucidated. In addition to hepcidin and systemic iron homeostatic control, iron metabolism can be controlled at cellular level though the mechanism involving iron responsive element (IRE) and iron responsive protein (IRP). Several iron-related mRNAs contain IRE(s) at 5’ or 3’ untranslated region (UTR) and the expression of the mRNAs can be controlled through the interaction between IRE and IRP whose IRE-binding activity is influenced by many factors including cellular iron level. Moreover, acute dietary iron deficiency can also regulate the expression of intestinal iron transporters and, subsequently, iron absorption through the action of hypoxia inducible 2 alpha (Hif-2a). Recent evidences suggest that enterocytes have intrinsic ability of regulate cellular iron homeostasis and subsequent iron absorption independently of hepcidin. My current interest is to delineate the mechanisms of hepcidin regulation by erythropoietic activity and ineffective erythropoiesis, particularly in thalassaemia. A thorough understanding of such mechanisms could potentially lead to the identification of therapeutic target(s) to manipulate iron status in thalassaemia patients. Furthermore, an investigation on therapeutic approach to thalassaemia and other iron overload conditions is also in near-future plan.