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ID 112882
Title Alternative
小腸のリン恒常性における小腸型アルカリホスファターゼ(Akp3)の役割について
Author
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
Narisawa, Sonoko Sanford Burnham Prebys Medical Discovery Institute
Millán, José Luis Sanford Burnham Prebys Medical Discovery Institute
Keywords
Hyperphosphatemia
CKD-MBD
Phosphate transporter
Content Type
Thesis or Dissertation
Description
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 adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration.
Journal Title
Kidney and Blood Pressure Research
ISSN
14204096
14230143
NCID
AA11085044
AA12783818
Publisher
S. Karger AG
Volume
43
Issue
5
Start Page
1409
End Page
1424
Published Date
2018-09-10
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Shohei Sasaki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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3220号
Diploma Number
甲栄第260号
Granted Date
2018-09-27
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences