Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City, Japan.
Am J Physiol Renal Physiol. 2011 Nov;301(5):F1105-13. doi: 10.1152/ajprenal.00663.2010. Epub 2011 Aug 3.
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.
无机磷酸盐（P(i)）限制饮食对慢性肾脏病患者和血液透析患者非常重要。磷结合剂对于预防高磷血症和异位钙化至关重要。钠依赖性 P(i)（Na/P(i)）转运系统参与肠道 P(i)吸收，并受多种因素调节。II 型钠依赖性 P(i)转运体 Npt2b 表达于肠道上皮细胞的刷状缘膜，并转运 P(i)。在本研究中，我们分析了 Npt2b(-/-)和杂合(+/-)小鼠的表型。Npt2b(-/-)小鼠在着床后不久即死于子宫内，表明 Npt2b 对于早期胚胎发育是必需的。在 4 周龄时，Npt2b(+/-)小鼠表现出低磷血症和低尿磷排泄。与 Npt2b(+/+)小鼠相比，Npt2b(+/-)小鼠的血浆成纤维细胞生长因子 23 水平显著降低，1,25(OH)(2)D(3)水平显著升高。Npt2b(+/-)小鼠的 Npt2b mRNA 水平降低至 Npt2b(+/+)小鼠的 50%。相比之下，Npt2b(+/-)小鼠的肾 Npt2a 和 Npt2c 转运蛋白水平显著升高。在 20 周龄时，Npt2b(+/-)小鼠出现低磷尿和远端肠道 Na/P(i)协同转运活性降低。用腺嘌呤诱导肾衰竭的 Npt2b(+/-)小鼠出现高磷血症和高血浆肌酐水平。用腺嘌呤处理的 Npt2b(+/-)小鼠的血浆 P(i)水平显著低于 Npt2b(+/+)小鼠。与 Npt2b(+/+)小鼠相比，Npt2b(+/-)小鼠的肠道 Npt2b 蛋白和 Na(+)/P(i)转运活性水平显著降低。本研究结果表明，Npt2b 是预防高磷血症的重要靶点。
