Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice

Author:

Li Huihui12,Choesang Tenzin3,Bao Weili3,Chen Huiyong34,Feola Maria25,Garcia-Santos Daniel6,Li Jie7,Sun Shuming34,Follenzi Antonia5,Pham Petra8,Liu Jing47,Zhang Jinghua7,Ponka Prem6,An Xiuli7,Mohandas Narla7,Fleming Robert E.9,Rivella Stefano10,Li Guiyuan1,Ginzburg Yelena Z.12

Affiliation:

1. Hunan Key Laboratory of Carcinogenesis and Cancer Invasion, Cancer Research Institute, Central South University, Ministry of Education, Changsha, China;

2. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY;

3. Erythropoiesis Laboratory, New York Blood Center, New York, NY;

4. State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, China;

5. University of Piemonte Orientale, Amedeo Avogadro, Novara, Italy;

6. Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, QC, Canada;

7. Laboratory of Membrane Biology, New York Blood Center, New York, NY;

8. Flow Cytometry Core Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY;

9. Saint Louis University, Saint Louis, MO; and

10. Children’s Hospital of Philadelphia, Philadelphia, PA

Abstract

Key Points Apotransferrin decreases TfR1 expression and alters TfR1 trafficking to normalize enucleation in β-thalassemic erythroid precursors. Decreased TfR1 upregulates hepcidin in an iron- and ERFE-independent manner, resulting in iron-restricted β-thalassemic erythropoiesis.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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