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Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin.

Authors: Gardenghi, S  Marongiu, MF  Ramos, P  Guy, E  Breda, L  Chadburn, A  Liu, Y  Amariglio, N  Rechavi, G  Rachmilewitz, EA  Breuer, W  Cabantchik, ZI  Wrighting, DM  Andrews, NC  De Sousa, M  Giardina, PJ  Grady, RW  Rivella, S 
Citation: Gardenghi S, etal., Blood. 2007 Jun 1;109(11):5027-35. Epub 2007 Feb 13.
Pubmed: (View Article at PubMed) PMID:17299088
DOI: Full-text: DOI:10.1182/blood-2006-09-048868

Progressive iron overload is the most salient and ultimately fatal complication of beta-thalassemia. However, little is known about the relationship among ineffective erythropoiesis (IE), the role of iron-regulatory genes, and tissue iron distribution in beta-thalassemia. We analyzed tissue iron content and iron-regulatory gene expression in the liver, duodenum, spleen, bone marrow, kidney, and heart of mice up to 1 year old that exhibit levels of iron overload and anemia consistent with both beta-thalassemia intermedia (th3/+) and major (th3/th3). Here we show, for the first time, that tissue and cellular iron distribution are abnormal and different in th3/+ and th3/th3 mice, and that transfusion therapy can rescue mice affected by beta-thalassemia major and modify both the absorption and distribution of iron. Our study reveals that the degree of IE dictates tissue iron distribution and that IE and iron content regulate hepcidin (Hamp1) and other iron-regulatory genes such as Hfe and Cebpa. In young th3/+ and th3/th3 mice, low Hamp1 levels are responsible for increased iron absorption. However, in 1-year-old th3/+ animals, Hamp1 levels rise and it is rather the increase of ferroportin (Fpn1) that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the iron overload of beta-thalassemia.

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RGD Object Information
RGD ID: 11041616
Created: 2016-03-24
Species: All species
Last Modified: 2016-03-24
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.