title: Hepcidin independent iron recycling in a mouse model of β-thalassaemia intermedia.
abstract: In conditions such as β-thalassaemia, stimulated erythropoiesis can reduce the expression of the iron regulatory hormone hepcidin, increasing both macrophage iron release and intestinal iron absorption and leading to iron loading. However, in certain conditions, sustained elevation of erythropoiesis can occur without an increase in body iron load. To investigate this in more detail, we made use of a novel mouse strain (RBC14), which exhibits mild β-thalassaemia intermedia with minimal iron loading. We compared iron homeostasis in RBC14 mice to that of Hbbth3/+mice, a more severe model of β-thalassaemia intermedia. Both mouse strains showed a decrease in plasma iron half-life, although the changes were less severe in RBC14 mice. Despite this, intestinal ferroportin and serum hepcidin levels were unaltered in RBC14 mice. In contrast, Hbbth3/+mice exhibited reduced serum hepcidin and increased intestinal ferroportin. However, splenic ferroportin levels were increased in both mouse strains. These data suggest that in low-grade chronic haemolytic anaemia, such as that seen in RBC14 mice, the increased erythroid iron requirements can be met through enhanced macrophage iron release without the need to increase iron absorption, implying that hepcidin is not the sole regulator of macrophage iron release in vivo.
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia. david.frazer@qimrberghofer.edu.au.
authors.forename: David M
authors.initials: DM
authors.lastname: Frazer
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wilkins
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.|Schools of Medicine, The University of Queensland, St Lucia, Australia.
authors.forename: Cornel S G
authors.initials: CS
authors.lastname: Mirciov
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Dunn
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, Herston, Australia. greg.anderson@qimrberghofer.edu.au.|Schools of Medicine, The University of Queensland, St Lucia, Australia. greg.anderson@qimrberghofer.edu.au.|School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia. greg.anderson@qimrberghofer.edu.au.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D015415:Biomarkers; D027682:Cation Transport Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015672:Erythroid Precursor Cells / Q000378:metabolism; D004920:Erythropoiesis; D005260:Female; D064451:Hepcidins / Q000097:blood / Q000378:metabolism*; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D055542:alpha-Globins / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000378:metabolism*; D000098742:Ferroportin
chemical_list: D015415:Biomarkers; D027682:Cation Transport Proteins; D064451:Hepcidins; D055542:alpha-Globins; D000098742:Ferroportin; D007501:Iron
keywords: ferroportin; hepcidin; iron homeostasis; iron recycling; β-thalassaemia