Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Kazuki Kawakami, Ai Takeshita, Kenryo Furushima, Masayasu Miyajima, Ikuji Hatamura, Makoto Kuro-O, Yasuhide Furuta, Kazushige Sakaguchi

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19 Scopus citations

Abstract

Secondary hyperparathyroidism, in which parathyroid hormone (PTH) is excessively secreted in response to factors such as hyperphosphataemia, hypocalcaemia, and low 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels, is commonly observed in patients with chronic kidney disease (CKD), and is accompanied by high levels of fibroblast growth factor 23 (FGF23). However, the effect of FGF23 on the parathyroid glands (PG) remains controversial. To bind to FGF receptors, FGF23 requires αKlotho, which is highly expressed in the PG. Here, we examined the effects of Fgfr1-3, αKlotho, or Fgfr1-4 ablation specifically in the PG (conditional knockout, cKO). When mice with early to mid-stage CKD with and without cKO were compared, plasma concentrations of calcium, phosphate, FGF23, and 1,25(OH) 2 D did not change significantly. In contrast, plasma PTH levels, which were elevated in CKD mice, were significantly decreased in cKO mice. PG from CKD mice showed augmentation of cell proliferation, which was significantly suppressed by cKO. Parathyroid tissue cultured for 4 days showed upregulation of PTH secretion and cell proliferation in response to FGF23. Both these effects were inhibited by cKO. These findings suggest that FGF23 is a long-Term inducer of parathyroid cell proliferation and PTH secretion, and is one cause of secondary hyperparathyroidism in CKD.

Original languageEnglish (US)
Article number40534
JournalScientific reports
Volume7
DOIs
StatePublished - Jan 17 2017

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    Kawakami, K., Takeshita, A., Furushima, K., Miyajima, M., Hatamura, I., Kuro-O, M., Furuta, Y., & Sakaguchi, K. (2017). Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease. Scientific reports, 7, [40534]. https://doi.org/10.1038/srep40534