Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules
Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules
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DOI：
10.1111/j.1523-1755.2005.00506.x
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发表时间：
2005-09-01
影响因子：
19.6
通讯作者：
Quigley, R
中科院分区：
文献类型：
--
作者：
Baum, M;Schiavi, S;Quigley, R
背景成纤维细胞生长因子-23（FGF-23）与肿瘤诱导的骨软化症、X连锁低磷血症和常染色体显性低磷血症性佝偻病的肾磷酸盐消耗有关。在这项体外微灌注研究中，我们检查了FGF-23的稳定突变体FGF 23 R176 Q是否损害体外灌注的兔近曲小管和近直小管中的磷酸盐转运。我们还检查了肝素（一种已知促进FGF与其受体结合的分子）是否是FGF 23 R176 Q转运作用所必需的。在肝素存在的情况下，FGF 23 R176 Q使近曲小管中的磷酸盐转运从10.8 +/- 2.0减少到9.9 +/- 1.9 pmol/mm/min，近直小管中的磷酸盐转运从1.0 +/- 0.2减少到0.8 +/- 0.2 pmol/mm/min（均P < 0.05）。在不存在肝素的情况下，FGF 23 R176 Q没有作用。将切碎的小鼠肾皮质组织在组织培养基中孵育3小时，在肝素存在的情况下（但不存在），刷状缘膜囊泡（BBMV）钠依赖性磷酸盐转运（NaPi-2A）蛋白丰度降低。这些数据表明，体外FGF 23 R176 Q对磷酸盐转运的抑制需要肝素。FGF 23 R176 Q的作用与BBMV NaPi-2A蛋白丰度的降低相关。
Background. Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal-dominant hypophosphatemic rickets.Methods. In this in vitro microperfusion study we examined if FGF23R176Q, a stable mutant of FGF-23, impairs phosphate transport in rabbit proximal convoluted and proximal straight tubules perfused in vitro. We also examined if heparin, a molecule that is known to facilitate binding of FGFs to their receptor was necessary for the action of FGF23R176Q on transport.Results. In the presence of heparin, FGF23R176Q reduced phosphate transport from 10.8 +/- 2.0 to 9.9 +/- 1.9 pmol/mm/min in proximal convoluted tubules and 1.0 +/- 0.2 to 0.8 +/- 0.2 pmol/mm/min in proximal straight tubules (both P < 0.05). There was no effect of FGF23R176Q in the absence of heparin. Incubation of finely minced mouse renal cortical tissue in tissue culture media for 3 hours resulted in a reduction in brush border membrane vesicles (BBMV) sodium-dependent phosphate transport (NaPi-2A) protein abundance in the presence but not in the absence of heparin.Conclusion. These data demonstrate that the inhibition of phosphate transport by FGF23R176Q in vitro requires heparin. The action of FGF23R176Q is associated with a reduction in BBMV NaPi-2A protein abundance.