A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

Autor: Takaaki Shimohata, José Luis Millán, Shohei Sasaki, Ai Hanazaki, Ruri Kirino, Toru Fujii, Kayo Ikuta, Yuji Shiozaki, Ichiro Kaneko, Sumire Sasaki, Hiroko Segawa, Miwa Noguchi, Sonoko Narisawa, Sawako Tatsumi, Ken-ichi Miyamoto, Megumi Koike, Yoshichika Kawai, Kazuya Tanifuji
Rok vydání: 2018
Předmět:
0301 basic medicine
Fibroblast growth factor 23
lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.medical_specialty
Brush border
030232 urology & nephrology
Parathyroid hormone
lcsh:RC870-923
Sodium-Phosphate Cotransporter Proteins
Type IIb
Article
Phosphates
Mice
03 medical and health sciences
Hyperphosphatemia
0302 clinical medicine
Internal medicine
CKD-MBD
lcsh:Dermatology
medicine
Animals
Homeostasis
Renal Insufficiency
Intestinal Mucosa
Mice
Knockout
Chemistry
Biological Transport
General Medicine
lcsh:RL1-803
lcsh:Diseases of the genitourinary system. Urology
Alkaline Phosphatase
medicine.disease
Small intestine
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Phosphate transporter
lcsh:RC666-701
Nephrology
Knockout mouse
Alkaline phosphatase
Cardiology and Cardiovascular Medicine
Zdroj: Kidney Blood Press Res
Kidney & Blood Pressure Research, Vol 43, Iss 5, Pp 1409-1424 (2018)
ISSN: 1423-0143
1420-4096
Popis: 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.
Databáze: OpenAIRE
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