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Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Maria L. Mace
  • Eva Gravesen
  • Anders Nordholm
  • Jacob Hofman-Bang
  • Thomas Secher
  • Ølgaard, Klaus
  • Ewa Lewin

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.

OriginalsprogEngelsk
TidsskriftKidney International
Vol/bind92
Udgave nummer1
Sider (fra-til)165-178
ISSN0085-2538
DOI
StatusUdgivet - jul. 2017

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