A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction.
Br J Haematol
; 168(6): 891-901, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25403101
ABSTRACT
Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron-deficiency anaemia and iron overload, is common in many clinical conditions and impacts the health of up to 30% of the world's population. The proteins transmembrane protease, serine 6 (TMPRSS6; also termed matriptase-2), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis, by regulating expression of the iron regulatory hormone hepcidin. We have performed a systematic analysis of mice deficient in these three proteins and show that TMPRSS6 predominates over HFE and TFR2 in hepcidin regulation. The phenotype of mice lacking TMPRSS6 and TFR2 is characterized by severe anaemia and extramedullary haematopoiesis in the spleen. Stress erythropoiesis in these mice results in increased expression of the newly identified erythroid iron regulator erythroferrone, which does not appear to overcome the hepcidin overproduction mediated by loss of TMPRSS6. Extended analysis reveals that TFR2 plays an important role in erythroid cells, where it is involved in terminal erythroblast differentiation and the regulation of erythropoietin. In conclusion, we have identified an essential role for TFR2 in erythropoiesis that may provide new targets for the treatment of anaemia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Agentes_cancerigenos
Base de dados:
MEDLINE
Assunto principal:
Receptores da Transferrina
/
Anemia Ferropriva
/
Eritropoese
Limite:
Animals
Idioma:
En
Revista:
Br J Haematol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Austrália