ナガノ　ノブオ   Nagano Nobuo   永野　伸郎    所属   医学部 医学科（附属足立医療センター）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：(1932-6203)1932-6203(Linking)
巻・号・頁	13(3),pp.e0191706
著者・共著者	Sugiura Hidekazu, Matsushita Ai, Futaya Mayuko, Teraoka Atsuko, Akiyama Ken-Ichi, Usui Noriyoshi, Nagano Nobuo, Nitta Kosaku, Tsuchiya Ken
発行年月	2018
概要	The hormone fibroblast growth factor 23 (FGF23) is secreted from bone and is involved in phosphorus (P) metabolism. FGF23 mainly binds the FGF receptor, which interacts with αKlotho in the kidney or parathyroid and regulates Na-dependent phosphate co-transporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) expression, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activity, and parathyroid hormone (PTH) secretion. In this study, we utilized hemi-nephrectomized rats fed a high-P diet (HP Nx), rats subjected to a partial nephrectomy (PN) and rats with doxorubicin-induced renal failure (DXR) as chronic kidney disease (CKD) animal models and analyzed the P metabolism and FGF23 expression in the kidneys in each CKD model. We cultured HK2 cells with a high level of P, 1,25(OH)2D3 or transforming growth factor-β1 (TGFβ1) to investigate the FGF23 expression mechanism. In both the HP Nx and PN rats, the blood FGF23 and PTH levels were increased. However, the 1,25(OH)2D3 level was increased in the HP Nx rats and decreased in the PN rats. In all three animal models, the mRNA expression of αKlotho, NaPi-IIa and NaPi-IIc was decreased, and the mRNA expression of TGFβ1, collagen1a1, osteopontin and FGF23 was elevated in the kidney. FGF23 protein and mRNA were expressed at high levels in the extended tubule epithelium, which was an osteopontin-positive region in the HP and PN rats. FGF23 and osteopontin mRNAs were expressed in HK2 cells incubated with TGFβ1; however, these levels were not altered in HK2 cells incubated with 1,25(OH)2D3 and high P levels in vitro. Altogether, FGF23 is expressed in the kidneys in CKD model rats. Following stimulation with TGFβ1, the injured renal tubular epithelial cells are strongly suspected to express both FGF23 and osteopontin. FGF23 produced in the kidney might contribute to P metabolism in subjects with CKD.
DOI	10.1371/journal.pone.0191706
PMID	29518087