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FASEB J. 2018 Jul;32(7):3752-3764. doi: 10.1096/fj.201700667R. Epub 2018 Feb 26.

Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia.

Author information

1
Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, USA.
2
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
3
Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; and.
4
Department of Medicine, New York University School of Medicine, New York, New York, USA.

Abstract

Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects. We previously reported that high fibroblast growth factor 23 (FGF23) levels in mice are associated with decreased red blood cell production, whereas genetic inactivation of Fgf23 results in expansion of the erythroid lineage. The present study is the first to show that high FGF23 levels in a mouse model of renal failure contribute to renal anemia, and inhibiting FGF23 signaling stimulates erythropoiesis and abolishes anemia and iron deficiency. Moreover, we show that inhibition of FGF23 signaling significantly decreases erythroid cell apoptosis and influences the commitment of hematopoietic stem cells toward the erythroid linage. Furthermore, we show that blocking FGF23 signaling attenuates inflammation, resulting in increased serum iron and ferritin levels. Our data clearly demonstrate that elevated FGF23 is a causative factor in the development of renal anemia and iron deficiency, and importantly, blocking FGF23 signaling represents a novel approach to stimulate erythropoiesis and possibly improve survival for millions of chronic kidney disease patients worldwide.-Agoro, R., Montagna, A., Goetz, R., Aligbe, O., Singh, G., Coe, L. M., Mohammadi, M., Rivella, S., Sitara, D. Inhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia.

KEYWORDS:

FGF23; chronic kidney disease; erythropoietin; iron

PMID:
29481308
PMCID:
PMC5998980
DOI:
10.1096/fj.201700667R
[Indexed for MEDLINE]

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