Signal networks among organ/tissue in the disorder of phosphate homeostasis

成纤维细胞生长因子23（Fibroblast growth factor 23，FGF 23）是一种骨源性激素，在近端肾小管细胞磷酸盐（phosphate，Pi）转运中起重要作用。 Klotho与FGF受体形成特异性受体复合物，其在远端小管中传递FGF 23的信号传导。FGF 23/klotho信号传导导致近端小管中钠依赖性Pi协同转运蛋白（NaPi-II）的下调。 本研究探讨了FGF 23/klotho系统下调肾Pi转运蛋白的机制以及骨细胞中FGF 23的产生。我们发现，klotho在近端小管的表达是由几个条件。此外，PKC对NaPi-IIc的失活是FGF 23/klotho依赖性转运蛋白下调的第一步。因此，肾-骨轴中的FGF 23/klotho信号传导对于Pi稳态是必不可少的。

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays an important role in phosphate (Pi) transport in the proximal tubular cells. Klotho forms a specific receptor complex with FGF receptor that transmits signaling of FGF23 in the distal tubules. FGF23/klotho signaling leads to down-regulation of sodium-dependent Pi cotransporter (NaPi-II ) in the proximal tubules. In the present study, we investigated the mechanisms of down-regulation of renal Pi transporter by FGF23/klotho system and the production of FGF23 in bone cells. We show that klotho expression in the proximal tubules is induced by several conditions. Furthermore, inactivation of NaPi-IIc by PKC is the first step of FGF23/klotho dependent down-regulation of the transporters. Thus, FGF23/klotho signaling in the kidney-bone axis is essential for Pi homeostasis.