Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia. / Mace, Maria L.; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa.
I: Kidney International, Bind 92, Nr. 1, 07.2017, s. 165-178.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia
AU - Mace, Maria L.
AU - Gravesen, Eva
AU - Nordholm, Anders
AU - Hofman-Bang, Jacob
AU - Secher, Thomas
AU - Olgaard, Klaus
AU - Lewin, Ewa
PY - 2017/7
Y1 - 2017/7
N2 - Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone.
AB - Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone.
KW - FGF23
KW - Hyperparathyroidism
KW - Mineral metabolism
KW - Phosphate
KW - Uremia
U2 - 10.1016/j.kint.2017.01.015
DO - 10.1016/j.kint.2017.01.015
M3 - Journal article
C2 - 28341272
AN - SCOPUS:85015743972
VL - 92
SP - 165
EP - 178
JO - Kidney International
JF - Kidney International
SN - 0085-2538
IS - 1
ER -
ID: 179164938