FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1
FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1
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DOI：
10.1152/ajprenal.90742.2008
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Baum, Michel
中科院分区：
文献类型：
--
作者：
Gattineni, Jyothsna;Bates, Carlton;Baum, Michel
[10]杨文军，李文军. FGF 23主要通过FGF受体1降低肾NaPi-2a和NaPi-2c表达并在体内诱导低磷酸盐血症。AmJ Physiol Renal Physiol 297：F282-F291，2009。首次发表于2009年6月10日; doi：10.1152/ajprenal.90742.2008。成纤维细胞生长因子-23（FGF 23）是一种磷酸尿激素，通过降低肾脏近端小管中II型磷酸钠协同转运蛋白（NaPi-2a和NaPi-2c）的表达和降低血清1，25-二羟维生素D-3 [1，25（OH）（2）D-3]水平，导致几种低磷酸盐血症疾病。体内介导FGF 23的低血磷作用的FGF受体仍然是难以捉摸的。在这项研究中，我们表明近端小管表达FGFR 1、-3和-4，但不表达FGFR 2 mRNA。为了确定这三种FGFR中的哪一种介导FGF 23的低血磷作用，我们表征了FGFR 3（-/-）和FGFR 4（-/-）缺失小鼠以及条件性FGFR 1（-/-）小鼠中的磷酸盐稳态，其中靶向删除后肾间充质中的FGFR 1表达。FGFR 1（-/-）、FGFR 3（-/-）和FGFR 4（-/-）小鼠及其野生型对应小鼠之间的基础血清磷水平和肾皮质刷状缘膜（BBM）NaPi-2a和NaPi-2c表达相当。给予FGFR 3（-/-）小鼠FGF 23诱导这些小鼠的低磷酸盐血症（8.0 +/- 0.4对5.4 +/- 0.3 mg/dl; p
Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, Mohammadi M, Baum M. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. AmJ Physiol Renal Physiol 297: F282-F291, 2009. First published June 10, 2009; doi:10.1152/ajprenal.90742.2008.-Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone that contributes to several hypophosphatemic disorders by reducing the expression of the type II sodium-phosphate cotransporters (NaPi-2a and NaPi-2c) in the kidney proximal tubule and by reducing serum 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] levels. The FGF receptor(s) mediating the hypophosphatemic action of FGF23 in vivo have remained elusive. In this study, we show that proximal tubules express FGFR1, -3, and -4 but not FGFR2 mRNA. To determine which of these three FGFRs mediates FGF23's hypophosphatemic actions, we characterized phosphate homeostasis in FGFR3(-/-) and FGFR4(-/-) null mice, and in conditional FGFR1(-/-) mice, with targeted deletion of FGFR1 expression in the metanephric mesenchyme. Basal serum phosphorus levels and renal cortical brush-border membrane (BBM) NaPi-2a and NaPi-2c expression were comparable between FGFR1(-/-), FGFR3(-/-), and FGFR4(-/-) mice and their wild-type counterparts. Administration of FGF23 to FGFR3(-/-) mice induced hypophosphatemia in these mice (8.0 +/- 0.4 vs. 5.4 +/- 0.3 mg/dl; p