FGF-23 is a negative regulator of prenatal and postnatal erythropoiesis

Lindsay M. Coe, Sangeetha Vadakke Madathil, Carla Casu, Beate Lanske, Stefano Rivella, Despina Sitara

Research output: Contribution to journalArticle

Abstract

Abnormal blood cell production is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD). Bonederived FGF-23 (fibroblast growth factor-23) regulates phosphate homeostasis and bone mineralization. Genetic deletion of Fgf-23 in mice (Fgf-23-/-) results in hypervitaminosis D, abnormal mineral metabolism, and reduced lymphatic organ size. Elevated FGF-23 levels are linked to CKD and greater risk of CVD, left ventricular hypertrophy, and mortality in dialysis patients. However, whether FGF-23 is involved in the regulation of erythropoiesis is unknown. Here we report that loss of FGF-23 results in increased hematopoietic stem cell frequency associated with increased erythropoiesis in peripheral blood and bone marrow in young adult mice. In particular, these hematopoietic changes are also detected in fetal livers, suggesting that they are not the result of altered bone marrow niche alone. Most importantly, administration of FGF-23 in wild-type mice results in a rapid decrease in erythropoiesis. Finally, we show that the effect of FGF-23 on erythropoiesis is independent of the high vitamin D levels in these mice. Our studies suggest a novel role for FGF-23 in erythrocyte production and differentiation and suggest that elevated FGF-23 levels contribute to the pathogenesis of anemia in patients with CKD and CVD.

Original languageEnglish (US)
Pages (from-to)9795-9810
Number of pages16
JournalJournal of Biological Chemistry
Volume289
Issue number14
DOIs
StatePublished - Apr 4 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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