TY - JOUR T1 - Pathways for the regulation of body iron homeostasis in response to experimental iron overload. JF - J Hepatol Y1 - 2005 A1 - Theurl, Igor A1 - Ludwiczek, Susanne A1 - Eller, Philipp A1 - Seifert, Markus A1 - Artner, Erika A1 - Peter Brunner A1 - Weiss, Günter KW - Animals KW - Disease Models, Animal KW - Disease Progression KW - DNA Primers KW - Duodenum KW - Gene Expression Regulation KW - Hepatocytes KW - Homeostasis KW - Iron KW - Iron Overload KW - Macrophages KW - Mice KW - Mice, Inbred C57BL KW - Polymerase Chain Reaction KW - RNA AB - BACKGROUND/AIMS: Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions. METHODS: To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days. RESULTS: Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced. CONCLUSIONS: Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation. VL - 43 UR - http://www.sciencedirect.com/science/article/pii/S0168827805003168# IS - 4 ER -