Format

Send to

Choose Destination
Kidney Int. 2018 May;93(5):1131-1141. doi: 10.1016/j.kint.2017.11.018. Epub 2018 Feb 1.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

Author information

1
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Division of Nephrology, Department of Medicine, Hospital Clinico Universidad de Chile, Santiago, Chile; Centro de Investigacion Clinica Avanzada, Hospital Clinico Universidad de Chile, Santiago, Chile.
2
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.
3
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
4
Millennium Institute on Immunology and Immunotherapy, Santiago, Chile; Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andrés Bello, Santiago, Chile.
5
Department of Obstetrics and Gynaecology, Faculty of Medicine, Universidad de los Andes, Santiago, Chile.
6
Tokyo Medical and Dental University, Tokyo, Japan.
7
Clinical Laboratory, Hospital Clinico Universidad de Chile, Santiago, Chile.
8
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago, Chile.
9
Critical Care Unit, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile.
10
Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Division of Nephrology, Department of Medicine, Hospital Clinico Universidad de Chile, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Santiago, Chile. Electronic address: lmichea@med.uchile.cl.

Abstract

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.

KEYWORDS:

FGF23; acute kidney injury; bone; erythropoietin; sepsis

PMID:
29395333
DOI:
10.1016/j.kint.2017.11.018
[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center