ID 113608
著者
Sasaki, Shohei University of Tokushima
Hanazaki, Ai University of Tokushima
Kirino, Ruri University of Tokushima
Fujii, Toru University of Tokushima
Ikuta, Kayo University of Tokushima
Noguchi, Miwa University of Tokushima
Sasaki, Sumire University of Tokushima
Koike, Megumi University of Tokushima
Tanifuji, Kazuya University of Tokushima
Shiozaki, Yuji University of Tokushima
Narisawa, Sonoko Sanford Burnham Prebys Medical Discovery Institute
Millán, José Luis Sanford Burnham Prebys Medical Discovery Institute
キーワード
Hyperphosphatemia
CKD-MBD
Phosphate transporter
資料タイプ
学術雑誌論文
抄録
Background/Aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration. Results: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenineinduced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration.
掲載誌名
Kidney and Blood Pressure Research
ISSN
14204096
14230143
cat書誌ID
AA11085044
AA12783818
出版者
Karger
43
5
開始ページ
1409
終了ページ
1424
発行日
2018-09-10
権利情報
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
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
出版社版
部局
医学系