Journal article
Erythropoietin stimulates fibroblast growth factor 23 (FGF23) in mice and men.
- Daryadel A University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Bettoni C University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Haider T Vetsuisse Faculty, Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
- Imenez Silva PH University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Schnitzbauer U University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Pastor-Arroyo EM University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Wenger RH University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
- Gassmann M Vetsuisse Faculty, Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland.
- Wagner CA University of Zurich, Institute of Physiology, Winterthurerstrasse 190, 8057, Zurich, Switzerland. Wagnerca@access.uzh.ch.
- 2018-07-03
Published in:
- Pflugers Archiv : European journal of physiology. - 2018
Bone
Erythropoietin
FGF23
Kidney
Mineral metabolism
Vitamin D3
Adult
Animals
Bone Marrow
Calcitriol
Cells, Cultured
Erythropoietin
Feedback, Physiological
Female
Fibroblast Growth Factors
Glucuronidase
Humans
Kidney
Male
Mice
Mice, Inbred C57BL
Parathyroid Hormone
Up-Regulation
English
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1007/s00424-018-2171-7
- PMID 29961920
- Persistent URL
- https://sonar.ch/global/documents/299027
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