title: FGF-23 is a negative regulator of prenatal and postnatal erythropoiesis.
abstract: Abnormal blood cell production is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD). Bone-derived 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.
authors: From the Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York 10010.
authors: Lindsay M
authors: LM
authors: Coe
authors: Sangeetha Vadakke
authors: SV
authors: Madathil
authors: Carla
authors: C
authors: Casu
authors: Beate
authors: B
authors: Lanske
authors: Stefano
authors: S
authors: Rivella
authors: Despina
authors: D
authors: Sitara
mesh_terms: D000740:Anemia / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D002454:Cell Differentiation / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology*; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D012307:Risk Factors; D014807:Vitamin D / Q000235:genetics / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Anemia; Bone; Bone Marrow; Erythrocyte; Erythropoeisis; FGF-23; Hematopoiesis; Kidney