Regulation of fibroblast growth factor 23 production in bone in uremic rats

Fumie Saji, Kazuhiro Shiizaki, Sachiko Shimada, Tadashi Okada, Ken Kunimoto, Toshifumi Sakaguchi, Ikuji Hatamura, Takashi Shigematsu

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background: Fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1α,25-dihydroxyvitamin D [1,25(OH)2D 3] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating FGF23, but the direct regulation of this elevation of FGF23 is incompletely understood. Method:We measured plasma parameters in uremic rats fed a high-phosphorus diet and then performed parathyroidectomy (PTX) to determine its effect. We also investigated FGF23 mRNA expression in various tissues to identify the major source of circulating FGF23. Result: The uremic rats displayed dramatic changes in plasma FGF23 levels, consistent with increased expression of FGF23 in bone. Elevated FGF23 was associated with phosphate and parathyroid hormone (PTH). After PTX, the elevated FGF23 had decreased, consistent with decreased expression of FGF23 in bone. Significant decreases in plasma FGF23 were associated with PTH and 1,25(OH)2D3, but not phosphate. Conclusion: Elevated plasma FGF23 levels in uremic rats reflect the increased expression of FGF23 in bone. The expression of FGF23 in bone may be regulated by a PTH-1,25(OH) 2D3 axis-dependent pathway and another PTH-dependent and 1,25(OH)2D3-independent pathway in uremic rats. The pathway may be decided by the degree of renal dysfunction.

Original languageEnglish (US)
JournalNephron - Physiology
Volume111
Issue number4
DOIs
StatePublished - May 2009

Fingerprint

Bone and Bones
Parathyroid Hormone
Phosphates
fibroblast growth factor 23
Parathyroidectomy
Chronic Renal Insufficiency
Phosphorus
Diet
Kidney
Messenger RNA

Keywords

  • Chronic kidney disease
  • Fibroblast growth factor 23
  • Parathyroid hormone
  • Phosphate
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Saji, F., Shiizaki, K., Shimada, S., Okada, T., Kunimoto, K., Sakaguchi, T., ... Shigematsu, T. (2009). Regulation of fibroblast growth factor 23 production in bone in uremic rats. Nephron - Physiology, 111(4). https://doi.org/10.1159/000210389

Regulation of fibroblast growth factor 23 production in bone in uremic rats. / Saji, Fumie; Shiizaki, Kazuhiro; Shimada, Sachiko; Okada, Tadashi; Kunimoto, Ken; Sakaguchi, Toshifumi; Hatamura, Ikuji; Shigematsu, Takashi.

In: Nephron - Physiology, Vol. 111, No. 4, 05.2009.

Research output: Contribution to journalArticle

Saji, F, Shiizaki, K, Shimada, S, Okada, T, Kunimoto, K, Sakaguchi, T, Hatamura, I & Shigematsu, T 2009, 'Regulation of fibroblast growth factor 23 production in bone in uremic rats', Nephron - Physiology, vol. 111, no. 4. https://doi.org/10.1159/000210389
Saji F, Shiizaki K, Shimada S, Okada T, Kunimoto K, Sakaguchi T et al. Regulation of fibroblast growth factor 23 production in bone in uremic rats. Nephron - Physiology. 2009 May;111(4). https://doi.org/10.1159/000210389
Saji, Fumie ; Shiizaki, Kazuhiro ; Shimada, Sachiko ; Okada, Tadashi ; Kunimoto, Ken ; Sakaguchi, Toshifumi ; Hatamura, Ikuji ; Shigematsu, Takashi. / Regulation of fibroblast growth factor 23 production in bone in uremic rats. In: Nephron - Physiology. 2009 ; Vol. 111, No. 4.
@article{1b4053b7dd4f47ed9f9a4624be988388,
title = "Regulation of fibroblast growth factor 23 production in bone in uremic rats",
abstract = "Background: Fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1α,25-dihydroxyvitamin D [1,25(OH)2D 3] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating FGF23, but the direct regulation of this elevation of FGF23 is incompletely understood. Method:We measured plasma parameters in uremic rats fed a high-phosphorus diet and then performed parathyroidectomy (PTX) to determine its effect. We also investigated FGF23 mRNA expression in various tissues to identify the major source of circulating FGF23. Result: The uremic rats displayed dramatic changes in plasma FGF23 levels, consistent with increased expression of FGF23 in bone. Elevated FGF23 was associated with phosphate and parathyroid hormone (PTH). After PTX, the elevated FGF23 had decreased, consistent with decreased expression of FGF23 in bone. Significant decreases in plasma FGF23 were associated with PTH and 1,25(OH)2D3, but not phosphate. Conclusion: Elevated plasma FGF23 levels in uremic rats reflect the increased expression of FGF23 in bone. The expression of FGF23 in bone may be regulated by a PTH-1,25(OH) 2D3 axis-dependent pathway and another PTH-dependent and 1,25(OH)2D3-independent pathway in uremic rats. The pathway may be decided by the degree of renal dysfunction.",
keywords = "Chronic kidney disease, Fibroblast growth factor 23, Parathyroid hormone, Phosphate, Vitamin D",
author = "Fumie Saji and Kazuhiro Shiizaki and Sachiko Shimada and Tadashi Okada and Ken Kunimoto and Toshifumi Sakaguchi and Ikuji Hatamura and Takashi Shigematsu",
year = "2009",
month = "5",
doi = "10.1159/000210389",
language = "English (US)",
volume = "111",
journal = "Nephron - Physiology",
issn = "1660-2137",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Regulation of fibroblast growth factor 23 production in bone in uremic rats

AU - Saji, Fumie

AU - Shiizaki, Kazuhiro

AU - Shimada, Sachiko

AU - Okada, Tadashi

AU - Kunimoto, Ken

AU - Sakaguchi, Toshifumi

AU - Hatamura, Ikuji

AU - Shigematsu, Takashi

PY - 2009/5

Y1 - 2009/5

N2 - Background: Fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1α,25-dihydroxyvitamin D [1,25(OH)2D 3] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating FGF23, but the direct regulation of this elevation of FGF23 is incompletely understood. Method:We measured plasma parameters in uremic rats fed a high-phosphorus diet and then performed parathyroidectomy (PTX) to determine its effect. We also investigated FGF23 mRNA expression in various tissues to identify the major source of circulating FGF23. Result: The uremic rats displayed dramatic changes in plasma FGF23 levels, consistent with increased expression of FGF23 in bone. Elevated FGF23 was associated with phosphate and parathyroid hormone (PTH). After PTX, the elevated FGF23 had decreased, consistent with decreased expression of FGF23 in bone. Significant decreases in plasma FGF23 were associated with PTH and 1,25(OH)2D3, but not phosphate. Conclusion: Elevated plasma FGF23 levels in uremic rats reflect the increased expression of FGF23 in bone. The expression of FGF23 in bone may be regulated by a PTH-1,25(OH) 2D3 axis-dependent pathway and another PTH-dependent and 1,25(OH)2D3-independent pathway in uremic rats. The pathway may be decided by the degree of renal dysfunction.

AB - Background: Fibroblast growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1α,25-dihydroxyvitamin D [1,25(OH)2D 3] metabolism. Patients with chronic kidney disease (CKD) have increased levels of circulating FGF23, but the direct regulation of this elevation of FGF23 is incompletely understood. Method:We measured plasma parameters in uremic rats fed a high-phosphorus diet and then performed parathyroidectomy (PTX) to determine its effect. We also investigated FGF23 mRNA expression in various tissues to identify the major source of circulating FGF23. Result: The uremic rats displayed dramatic changes in plasma FGF23 levels, consistent with increased expression of FGF23 in bone. Elevated FGF23 was associated with phosphate and parathyroid hormone (PTH). After PTX, the elevated FGF23 had decreased, consistent with decreased expression of FGF23 in bone. Significant decreases in plasma FGF23 were associated with PTH and 1,25(OH)2D3, but not phosphate. Conclusion: Elevated plasma FGF23 levels in uremic rats reflect the increased expression of FGF23 in bone. The expression of FGF23 in bone may be regulated by a PTH-1,25(OH) 2D3 axis-dependent pathway and another PTH-dependent and 1,25(OH)2D3-independent pathway in uremic rats. The pathway may be decided by the degree of renal dysfunction.

KW - Chronic kidney disease

KW - Fibroblast growth factor 23

KW - Parathyroid hormone

KW - Phosphate

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=67649099265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649099265&partnerID=8YFLogxK

U2 - 10.1159/000210389

DO - 10.1159/000210389

M3 - Article

C2 - 19339809

AN - SCOPUS:67649099265

VL - 111

JO - Nephron - Physiology

JF - Nephron - Physiology

SN - 1660-2137

IS - 4

ER -