The fibroblast growth factor receptor mediates the increased FGF23 expression in acute and chronic uremia

Serum FGF23 is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. FGF23 expression is increased by activation of the FGF receptor 1 (FGFR1) in rats with normal renal function and in vitro in bone-derived osteoblast-like cells. We studied the regulation...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2016-02, Vol.310 (3), p.F217-F221
Main Authors: Hassan, Alia, Durlacher, Karina, Silver, Justin, Naveh-Many, Tally, Levi, Ronen
Format: Article
Language:English
Subjects:
Acute Kidney Injury - blood
Acute Kidney Injury - chemically induced
Acute Kidney Injury - genetics
Acute Kidney Injury - metabolism
Adenine
Animals
Cells
Chronic Disease
Disease Models, Animal
Fibroblast Growth Factors - blood
Fibroblast Growth Factors - genetics
Folic Acid
Kidney diseases
Male
Mice, Inbred C57BL
Osteocytes - drug effects
Osteocytes - metabolism
Parathyroid Hormone - blood
Phosphorus
Phosphorus, Dietary
Pyrimidines - pharmacology
Rats, Sprague-Dawley
Receptor, Fibroblast Growth Factor, Type 1 - antagonists & inhibitors
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Receptor, Fibroblast Growth Factor, Type 1 - metabolism
Ribonucleic acid
RNA
RNA, Messenger - metabolism
Rodents
Skull - drug effects
Skull - metabolism
Up-Regulation
Uremia - blood
Uremia - chemically induced
Uremia - genetics
Uremia - metabolism
Vitamin B
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Summary:Serum FGF23 is markedly elevated in chronic kidney disease and has been associated with poor long-term outcomes. FGF23 expression is increased by activation of the FGF receptor 1 (FGFR1) in rats with normal renal function and in vitro in bone-derived osteoblast-like cells. We studied the regulation of FGF23 by FGFR1 in vivo in acute and chronic uremia in mice and rats. Folic acid-induced acute kidney injury increased calvaria FGF23 mRNA and serum FGF23 and parathyroid hormone (PTH) levels at 6 h. The FGFR1 receptor inhibitor PD173074 prevented the folic acid-induced increase in both FGF23 mRNA and serum levels but had no effect on serum PTH levels. A more prolonged uremia due to an adenine high-phosphorus diet for 14 days resulted in high levels of FGF23 mRNA and serum FGF23 and PTH. PD173074 decreased serum FGF23 and mRNA levels with no effect on PTH in the adenine high phosphorus-induced uremic rats. Therefore, a derangement in FGF23 regulation starts early in the course of acute kidney injury, is in part independent of the increase in serum PTH, and involves activation of FGFR1. It is possible that FGFR1 in the osteocyte is activated by locally produced canonical FGFs, which are increased in uremia. This is the first demonstration that activation of FGFR1 is essential for the high levels of FGF23 in acute and chronic experimental uremia.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00332.2015