Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia
Joint Authors
Belo, Luís
Fernandes, João
Ribeiro, Sandra
Bronze-da-Rocha, E.
Rocha-Pereira, Petronila
Santos-Silva, Alice
Garrido, Patrícia
Costa, Elísio
Reis, Flávio
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-12-17
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Erythroid hypoplasia (EH) is a rare complication associated with recombinant human erythropoietin (rHuEPO) therapies, due to development of anti-rHuEPO antibodies; however, the underlying mechanisms remain poorly clarified.
Our aim was to manage a rat model of antibody-mediated EH induced by rHuEPO and study the impact on iron metabolism and erythropoiesis.
Wistar rats treated during 9 weeks with a high rHuEPO dose (200 IU) developed EH, as shown by anemia, reduced erythroblasts, reticulocytopenia, and plasmatic anti-rHuEPO antibodies.
Serum iron was increased and associated with mRNA overexpression of hepatic hepcidin and other iron regulatory mediators and downregulation of matriptase-2; overexpression of divalent metal transporter 1 and ferroportin was observed in duodenum and liver.
Decreased EPO expression was observed in kidney and liver, while EPO receptor was overexpressed in liver.
Endogenous EPO levels were normal, suggesting that anti-rHuEPO antibodies blunted EPO function.
Our results suggest that anti-rHuEPO antibodies inhibit erythropoiesis causing anemia.
This leads to a serum iron increase, which seems to stimulate hepcidin expression despite no evidence of inflammation, thus suggesting iron as the key modulator of hepcidin synthesis.
These findings might contribute to improving new therapeutic strategies against rHuEPO resistance and/or development of antibody-mediated EH in patients under rHuEPO therapy.
American Psychological Association (APA)
Fernandes, João& Garrido, Patrícia& Ribeiro, Sandra& Rocha-Pereira, Petronila& Bronze-da-Rocha, E.& Belo, Luís…[et al.]. 2014. Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia. BioMed Research International،Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1034460
Modern Language Association (MLA)
Fernandes, João…[et al.]. Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia. BioMed Research International No. 2014 (2014), pp.1-10.
https://search.emarefa.net/detail/BIM-1034460
American Medical Association (AMA)
Fernandes, João& Garrido, Patrícia& Ribeiro, Sandra& Rocha-Pereira, Petronila& Bronze-da-Rocha, E.& Belo, Luís…[et al.]. Iron as the Key Modulator of Hepcidin Expression in Erythroid Antibody-Mediated Hypoplasia. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1034460
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1034460