Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice
| Autor: | Akiko Ohi, Shinsuke Kido, Naoshi Horiba, Yumiko Oikawa, Hiromi Tateishi, Junya Furutani, Kou-ichi Jishage, Tomo Mukai, Ken-ichi Miyamoto, Hiroko Segawa, Naoko A. Wada, Kaoru Matsumoto, Mami Kakefuda, Ichiro Kaneko, Yousuke Kawase, Etsuyo Hanabusa, Shohei Sasaki, Otoya Ueda, Shoji Kuwahara, Fumito Aranami, Rieko Tominaga, Shuichi Ohtomo, Takanori Tachibe, Sawako Tatsumi, Naoshi Fukushima |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Chromosomes Artificial Bacterial Genotype Physiology medicine.medical_treatment Blotting Western Genetic Vectors Polymerase Chain Reaction Sodium-Phosphate Cotransporter Proteins Type IIb Phosphates chemistry.chemical_compound Hyperphosphatemia Mice Pregnancy Internal medicine medicine Animals Homeostasis Renal Insufficiency Intestinal Mucosa Mice Knockout Microvilli Adenine Sodium-Phosphate Cotransporter Proteins Body Weight Sodium Transporter DNA medicine.disease Phosphate Diet Mice Inbred C57BL Endocrinology chemistry Female Hemodialysis Cotransporter Kidney disease |
| Zdroj: | American journal of physiology. Renal physiology. 301(5) |
| ISSN: | 1522-1466 |
| Popis: | An inorganic phosphate (Pi)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent Pi(Na/Pi) transport system is involved in intestinal Piabsorption and is regulated by several factors. The type II sodium-dependent Pitransporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports Pi. In the present study, we analyzed the phenotype of Npt2b−/−and hetero+/−mice. Npt2b−/−mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b+/−mice showed hypophosphatemia and low urinary Piexcretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)2D3levels were significantly increased in Npt2b+/−mice compared with Npt2b+/+mice. Npt2b mRNA levels were reduced to 50% that in Npt2b+/+mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b+/−mice. At 20 wk of age, Npt2b+/−mice showed hypophosphaturia and reduced Na/Picotransport activity in the distal intestine. Npt2b+/+mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b+/−mice treated with adenine had significantly reduced plasma Pilevels compared with Npt2b+/+mice. Intestinal Npt2b protein and Na+/Pitransport activity levels were significantly lower in Npt2b+/−mice than in the Npt2b+/+mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia. |
| Databáze: | OpenAIRE |
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