Inhibition of fibroblast growth factor 23 (fgf23) signaling rescues renal anemia

Rafiou Agoro, Anna Montagna, Regina Goetz, Onyedikachi Aligbe, Gurinder Singh, Lindsay M. Coe, Moosa Mohammadi, Stefano Rivella, Despina Sitara

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3752-3764
Number of pages13
JournalFASEB Journal
Volume32
Issue number7
DOIs
StatePublished - Jul 2018

Keywords

  • Chronic kidney disease
  • Erythropoietin
  • FGF23
  • Iron

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Agoro, R., Montagna, A., Goetz, R., Aligbe, O., Singh, G., Coe, L. M., Mohammadi, M., Rivella, S., & Sitara, D. (2018). Inhibition of fibroblast growth factor 23 (fgf23) signaling rescues renal anemia. FASEB Journal, 32(7), 3752-3764. https://doi.org/10.1096/fj.201700667R