Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia.
Inherited anemias with ineffective erythropoiesis, such as β-thalassemia, manifest inappropriately low hepcidin production and consequent excessive absorption of dietary iron, leading to iron overload. Erythroferrone (ERFE) is an erythroid regulator of hepcidin synthesis and iron homeostasis. Erfe expression was highly increased in the marrow and spleen of Hbb(Th3/+) mice (Th3/+), a mouse model of thalassemia intermedia. Ablation of Erfe in Th3/+ mice restored normal levels of circulating hepcidin at 6 weeks of age, suggesting ERFE could be a factor suppressing hepcidin production in β-thalassemia. We examined the expression of Erfe and the consequences of its ablation in thalassemic mice from 3 to 12 weeks of age. The loss of ERFE in thalassemic mice led to full restoration of hepcidin mRNA expression at 3 and 6 weeks of age, and significant reduction in liver and spleen iron content at 6 and 12 weeks of age. Ablation of Erfe slightly ameliorated ineffective erythropoiesis, as indicated by reduced spleen index, red cell distribution width, and mean corpuscular volume, but did not improve the anemia. Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of β-thalassemia.
Department of Medicine and.
Léon
L
Kautz
Department of Medicine and.
Grace
G
Jung
Silarus Therapeutics, La Jolla, CA.
Xin
X
Du
Department of Medicine and.
Victoria
V
Gabayan
Silarus Therapeutics, La Jolla, CA.
Justin
J
Chapman
Silarus Therapeutics, La Jolla, CA.
Marc
M
Nasoff
Department of Medicine and.
Elizabeta
E
Nemeth
Department of Medicine and Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA; and.
Tomas
T
Ganz
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004920:Erythropoiesis / Q000502:physiology; D005260:Female; D064451:Hepcidins / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017086:beta-Thalassemia / Q000150:complications* / Q000235:genetics / Q000473:pathology*
D016207:Cytokines; C572502:Erfe protein, mouse; D064451:Hepcidins; D009124:Muscle Proteins; D012333:RNA, Messenger