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
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U2 - 10.1159/000210389
DO - 10.1159/000210389
M3 - Article
C2 - 19339809
AN - SCOPUS:67649099265
SN - 1660-2137
VL - 111
SP - p61-p68
JO - Nephron - Physiology
JF - Nephron - Physiology
IS - 4
ER -