The second transferrin receptor regulates red blood cell production in mice

Antonella Nai, Maria Rosa Lidonnici, Marco Rausa, Giacomo Mandelli, Alessia Pagani, Laura Silvestri, Giuliana Ferrari, Clara Camaschella

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Transferrin receptor 2 (TFR2) contributes to hepcidin regulation in the liver and associates with erythropoietin receptor in erythroid cells. Nevertheless, TFR2 mutations cause iron overload (hemochromatosis type 3) without overt erythroid abnormalities. To clarify TFR2 erythroid function, we generated a mouse lacking Tfr2 exclusively in the bone marrow (Tfr2BMKO). Tfr2BMKO mice have normal iron parameters, reduced hepcidin levels, higher hemoglobin and red blood cell counts, and lower mean corpuscular volume than normal control mice, a phenotype that becomes more evident in iron deficiency. In Tfr2BMKO mice, the proportion of nucleated erythroid cells in the bone marrow is higher and the apoptosis lower than in controls, irrespective of comparable erythropoietin levels. Induction of moderate iron deficiency increases erythroblasts number, reduces apoptosis, and enhances erythropoietin (Epo) levels in controls, but not in Tfr2BMKO mice. Epo-target genes such as Bcl-xL and Epor are highly expressed in the spleen and in isolated erythroblasts from Tfr2BMKO mice. Low hepcidin expression in Tfr2BMKO is accounted for by erythroid expansion and production of the erythroid regulator erythroferrone. We suggest that Tfr2 is a component of a novel iron-sensing mechanism that adjusts erythrocyte production according to iron availability, likely by modulating the erythroblast Epo sensitivity.

Original languageEnglish
Pages (from-to)1170-1179
Number of pages10
JournalBlood
Volume125
Issue number7
DOIs
Publication statusPublished - Feb 12 2015

Fingerprint

Transferrin Receptors
Blood
Iron
Erythrocytes
Cells
Hepcidins
Erythropoietin
Erythroblasts
Erythroid Cells
Bone
Bone Marrow
Apoptosis
Erythropoietin Receptors
Erythrocyte Count
Iron Overload
Erythrocyte Indices
Liver
Hemoglobins
Spleen
Genes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Nai, A., Lidonnici, M. R., Rausa, M., Mandelli, G., Pagani, A., Silvestri, L., ... Camaschella, C. (2015). The second transferrin receptor regulates red blood cell production in mice. Blood, 125(7), 1170-1179. https://doi.org/10.1182/blood-2014-08-596254

The second transferrin receptor regulates red blood cell production in mice. / Nai, Antonella; Lidonnici, Maria Rosa; Rausa, Marco; Mandelli, Giacomo; Pagani, Alessia; Silvestri, Laura; Ferrari, Giuliana; Camaschella, Clara.

In: Blood, Vol. 125, No. 7, 12.02.2015, p. 1170-1179.

Research output: Contribution to journalArticle

Nai, A, Lidonnici, MR, Rausa, M, Mandelli, G, Pagani, A, Silvestri, L, Ferrari, G & Camaschella, C 2015, 'The second transferrin receptor regulates red blood cell production in mice', Blood, vol. 125, no. 7, pp. 1170-1179. https://doi.org/10.1182/blood-2014-08-596254
Nai A, Lidonnici MR, Rausa M, Mandelli G, Pagani A, Silvestri L et al. The second transferrin receptor regulates red blood cell production in mice. Blood. 2015 Feb 12;125(7):1170-1179. https://doi.org/10.1182/blood-2014-08-596254
Nai, Antonella ; Lidonnici, Maria Rosa ; Rausa, Marco ; Mandelli, Giacomo ; Pagani, Alessia ; Silvestri, Laura ; Ferrari, Giuliana ; Camaschella, Clara. / The second transferrin receptor regulates red blood cell production in mice. In: Blood. 2015 ; Vol. 125, No. 7. pp. 1170-1179.
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