ID 112958
タイトル別表記
骨細胞除去による無機リン代謝における影響 : 骨-腎臓-腸管連関の解析
Phosphate Homeostasis and Osteocyte Ablation
著者
藤井, 理 徳島大学大学院栄養生命科学教育部(人間栄養科学専攻)
Ogata, Mao Tokushima University
Arakaki, Tomohiro Tokushima University
Sakaguchi, Haruna Tokushima University
Nomura, Kengo Tokushima University
Miyagawa, Atsumi Tokushima University
Ikuta, Kayo Tokushima University
Hanazaki, Ai Tokushima University
キーワード
osteocyte
phosphate
fibroblast growth factor 23
Klotho
intestine
kidney
liver
bile acid
資料タイプ
学位論文
抄録
In response to kidney damage, osteocytes increase the production of several hormones critically involved in mineral metabolism. Recent studies suggest that osteocyte function is altered very early in the course of chronic kidney disease. In the present study, to clarify the role of osteocytes and the canalicular network in mineral homeostasis, we performed four experiments. In Experiment 1, we investigated renal and intestinal Pi handling in osteocyte-less (OCL) model mice [transgenic mice with the dentin matrix protein-1 promoter-driven diphtheria toxin (DT)-receptor that were injected with DT]. In Experiment 2, we administered granulocyte colony-stimulating factor to mice to disrupt the osteocyte canalicular network. In Experiment 3, we investigated the role of osteocytes in dietary Pi signaling. In Experiment 4, we analyzed gene expression level fluctuations in the intestine and liver by comparing mice fed a high Pi diet and OCL mice. Together, the findings of these experiments indicate that osteocyte ablation caused rapid renal Pi excretion (P < 0.01) before the plasma fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) levels increased. At the same time, we observed a rapid suppression of renal Klotho (P < 0.01), type II sodium phosphate transporters Npt2a (P < 0.01) and Npt2c (P < 0.05), and an increase in intestinal Npt2b (P < 0.01) protein. In OCL mice, Pi excretion in feces was markedly reduced (P < 0.01). Together, these effects of osteocyte ablation are predicted to markedly increase intestinal Pi absorption (P < 0.01), thus suggesting that increased intestinal Pi absorption stimulates renal Pi excretion in OCL mice. In addition, the ablation of osteocytes and feeding of a high Pi diet affected FGF15/bile acid metabolism and controlled Npt2b expression. In conclusion, OCL mice exhibited increased renal Pi excretion due to enhanced intestinal Pi absorption. We discuss the role of FGF23–Klotho on renal and intestinal Pi metabolism in OCL mice.
掲載誌名
Frontiers in Endocrinology
ISSN
16642392
出版者
Frontiers
8
開始ページ
359
発行日
2017-12-21
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Osamu Fujiiの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
© 2017 Fujii, Tatsumi, Ogata, Arakaki, Sakaguchi, Nomura, Miyagawa, Ikuta, Hanazaki, Kaneko, Segawa and Miyamoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3140号
学位記番号
甲栄第249号
学位授与年月日
2018-03-23
学位名
博士(栄養学)
学位授与機関
徳島大学
部局
医学系