title: Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice.
abstract: An inorganic phosphate (P(i))-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 P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). 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 P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels 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/P(i) cotransport 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 P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport 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.
authors.affiliation: Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohi
authors.forename: Etsuyo
authors.initials: E
authors.lastname: Hanabusa
authors.forename: Otoya
authors.initials: O
authors.lastname: Ueda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Segawa
authors.forename: Naoshi
authors.initials: N
authors.lastname: Horiba
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kaneko
authors.forename: Shoji
authors.initials: S
authors.lastname: Kuwahara
authors.forename: Tomo
authors.initials: T
authors.lastname: Mukai
authors.forename: Shohei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Rieko
authors.initials: R
authors.lastname: Tominaga
authors.forename: Junya
authors.initials: J
authors.lastname: Furutani
authors.forename: Fumito
authors.initials: F
authors.lastname: Aranami
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohtomo
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Kawase
authors.forename: Naoko A
authors.initials: NA
authors.lastname: Wada
authors.forename: Takanori
authors.initials: T
authors.lastname: Tachibe
authors.forename: Mami
authors.initials: M
authors.lastname: Kakefuda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tateishi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Sawako
authors.initials: S
authors.lastname: Tatsumi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kido
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Kou-Ichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000225:Adenine; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004247:DNA / Q000235:genetics; D004032:Diet; D005260:Female; D005822:Genetic Vectors; D005838:Genotype; D006706:Homeostasis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics* / Q000502:physiology*
chemical_list: D010710:Phosphates; C493558:Slc34a2 protein, mouse; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D004247:DNA; D012964:Sodium; D000225:Adenine