Intravenous phosphate loading increases fibroblast growth factor 23 in uremic rats.
Intravenous phosphate loading increases fibroblast growth factor 23 in uremic rats.
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DOI：
10.1371/journal.pone.0091096
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Akizawa T
中科院分区：
文献类型：
--
作者：
Arai-Nunota N;Mizobuchi M;Ogata H;Yamazaki-Nakazawa A;Kumata C;Kondo F;Hosaka N;Koiwa F;Kinugasa E;Shibata T;Akizawa T
口服磷酸盐负荷和骨化三醇刺激成纤维细胞生长因子 23 (FGF23) 分泌，但刺激 FGF23 的机制仍有待研究。我们比较了静脉磷酸盐负荷和口服磷酸盐负荷对正常和 5/6 肾切除尿毒症大鼠 FGF23 水平的影响。尿毒症大鼠（Nx）和假手术大鼠喂食正常磷酸盐饮食2周，然后分为3组：1）相同磷酸盐饮食（NP），2）高磷酸盐饮食（HP），3）NP大鼠使用微量输液泵静脉注射磷酸盐（IV）。干预后1天（早期）和7天（晚期）采集血液和尿液。在早期和晚期，Sham 和 Nx 大鼠的 HP 组和 IV 组的血清磷酸盐水平和磷酸盐排泄分数 (FEP) 相当。仅在 Nx 大鼠的晚期阶段，HP 组和 IV 组的血清磷酸盐水平与 NP 组相同且显着升高。在 Nx 大鼠的早期阶段，NP、HP 和 IV 组的 FGF23 水平相当，但在后期，HP 和 IV 组的 FGF23 水平显着高于 NP 组。与 NP 组相比，HP 组和 IV 组 Nx 大鼠肾脏中 1α-羟化酶和钠依赖性磷酸盐协同转运蛋白 2a 的表达水平同等显着降低，而 24-羟化酶表达水平同等显着升高。这些结果表明，慢性静脉内磷酸盐负荷会增加生物活性 FGF23，表明除了饮食途径外，可能还存在 FGF23 调节的替代途径。在磷酸盐容易超载的肾损伤造成的情况下，该途径更加清晰。
Oral phosphate loading and calcitriol stimulate Fibroblast growth factor 23 (FGF23) secretion, but the mechanisms underlying the stimulation of FGF23 remain to be studied. We compared the effect of intravenous phosphate loading with that of oral loading on FGF23 levels in normal and 5/6 nephrectomized uremic rats. Uremic rats (Nx) and sham-operated rats were fed a normal phosphate diet for 2 weeks and then divided into 3 groups: 1) with the same phosphate diet (NP), 2) with a high phosphate diet (HP), and 3) NP rats with intravenous phosphate infusion using a microinfusion pump (IV). Blood and urine were obtained 1 day (early phase) and 7 days (late phase) after the interventions. In the early and late phases, serum phosphate levels and fractional excretion of phosphate (FEP) were comparable in the HP and IV groups in both Sham and Nx rats. Serum phosphate levels in the HP and IV groups were equally and significantly higher than those in the NP group only in the late phase in Nx rats. In the early phase, FGF23 levels were comparable in the NP, HP, and IV groups, but were significantly higher in the HP and IV groups compared to the NP group in the late phase in Nx rats. 1α-hydroxylase and sodium dependent phosphate co-transporter 2a expression levels in the kidney in Nx rats were equally and significantly decreased in the HP and IV groups compared with the NP group, while 24-hydroxylase expression was equally and significantly increased. These results show that chronic intravenous phosphate loading increases bioactive FGF23, indicating that an alternative pathway for FGF23 regulation, in addition to the dietary route, may be present. This pathway is clearer under conditions produced by a kidney injury in which phosphate is easily overloaded.
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DOI：
10.1056/nejmoa0706130
发表时间：
2008-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Gutiérrez OM;Mannstadt M;Isakova T;Rauh-Hain JA;Tamez H;Shah A;Smith K;Lee H;Thadhani R;Jüppner H;Wolf M
通讯作者：
Wolf M
影响因子：
33.6
作者：
Martin A;David V;Quarles LD
通讯作者：
Quarles LD
影响因子：
4.8
作者：
Perwad, F;Azam, N;Portale, AA
通讯作者：
Portale, AA
影响因子：
56.9
作者：
HUGHES, MR;BRUMBAUGH, PF;BAYLINK, DJ
通讯作者：
BAYLINK, DJ
DOI：
10.1073/pnas.0704446104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Berndt, Theresa;Thomas, Leslie F.;Kumar, Rajiv
通讯作者：
Kumar, Rajiv