Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men

Daryadel, Arezoo; Bettoni, Carla; Haider, Thomas; Imenez Silva, Pedro H; Schnitzbauer, Udo; Pastor-Arroyo, Eva Maria; Wenger, Roland H; Gassmann, Max; Wagner, Carsten A (2018). Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men. Pflügers Archiv : European Journal of Physiology, 470(10):1569-1582.

Abstract

Fibroblast growth factor 23 (FGF23) is a major endocrine regulator of phosphate and 1,25 (OH)2 vitamin D3 metabolism and is mainly produced by osteocytes. Its production is upregulated by a variety of factors including 1,25 (OH)2 vitamin D3, high dietary phosphate intake, and parathyroid hormone (PTH). Recently, iron deficiency and hypoxia have been suggested as additional regulators of FGF23 and a role of erythropoietin (EPO) was shown. However, the regulation of FGF23 by EPO and the impact on phosphate and 1,25(OH)2 vitamin D3 are not completely understood. Here, we demonstrate that acute administration of recombinant human EPO (rhEPO) to healthy humans increases the C-terminal fragment of FGF23 (C-terminal FGF23) but not intact FGF23 (iFGF23). In mice, rhEPO stimulates acutely (24 h) C-terminal FGF23 but iFGF23 only after 4 days without effects on PTH and plasma phosphate. 1,25 (OH)2 D3 levels and αklotho expression in the kidney decrease after 4 days. rhEPO induced FGF23 mRNA in bone marrow but not in bone, with increased staining of FGF23 in CD71+ erythroid precursors in bone marrow. Chronic elevation of EPO in transgenic mice increases iFGF23. Finally, acute injections of recombinant FGF23 reduced renal EPO mRNA expression. Our data demonstrate stimulation of FGF23 levels in mice which impacts mostly on 1,25 (OH)2 vitamin D3 levels and metabolism. In humans, EPO is mostly associated with the C-terminal fragment of FGF23; in mice, EPO has a time-dependent effect on both FGF23 forms. EPO and FGF23 may form a feedback loop controlling and linking erythropoiesis and mineral metabolism.

Additional indexing

Contributors:National Center of Competence in Research NCCR Kidney.CH, Zürich, Switzerland
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Physiology
Life Sciences > Clinical Biochemistry
Health Sciences > Physiology (medical)
Uncontrolled Keywords:Bone, Erythropoietin, FGF23, Kidney, Mineral metabolism, Vitamin D3
Language:English
Date:2 July 2018
Deposited On:25 Jul 2018 15:26
Last Modified:24 Aug 2024 03:37
Publisher:Springer
ISSN:0031-6768
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00424-018-2171-7
PubMed ID:29961920
Project Information:
  • Funder: SNSF
  • Grant ID: 31003A_176125
  • Project Title: Molecular mechanisms of mammalian phosphate sensing and homeostatic control
  • Funder: SNSF
  • Grant ID: 31003A_165679
  • Project Title: Hydroxylation-dependent functions of OTUB1 in oxygen physiology
  • Funder: SNSF
  • Grant ID: 31003A_156481
  • Project Title: Reduced incidence of cancer at high altitude: analyzing the impact of hypoxia on tumor development
  • Funder: National Center for Competence in Research NCCR Kidney.Ch
  • Grant ID:
  • Project Title:
Download PDF  'Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men'.
Preview
  • Content: Accepted Version

Metadata Export

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

378 downloads since deposited on 25 Jul 2018
76 downloads since 12 months
Detailed statistics

Authors, Affiliations, Collaborations

Similar Publications