Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro.
Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro.
复制标题
成纤维细胞生长因子 23 可增加小鼠体内和体外 PGE2 的产生。
DOI：
10.1152/ajprenal.00234.2005
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Baum,Michel
中科院分区：
文献类型：
--
作者：
Syal,Ashu;Schiavi,Susan;Chakravarty,Sumana;Dwarakanath,Vangipuram;Quigley,Raymond;Baum,Michel
成纤维细胞生长因子 23 (FGF-23) 与 X 连锁低磷血症、肿瘤诱发的骨软化症和常染色体显性低磷血症性佝偻病中的肾磷酸盐消耗有关。最近，我们证明与 C57/B6 小鼠相比，Hypmice 具有更高的尿 PGE2 水平，并且体内和体外给予吲哚美辛可改善 Hypmice 的磷酸盐转运缺陷。为了进一步确定改变的前列腺素代谢是否在Hypmice的肾磷酸盐转运缺陷中发挥作用，我们用花生四烯酸孵育肾近端小管。我们发现 Hypmice 小鼠的 PGE2 产量高于 C57/B6 小鼠。将 C57/B6 小鼠肾近曲小管与 FGF-23R176Q（FGR23 的一种活性突变体形式）一起孵育，会增加肾小管 PGE2 的产生，而这种作用可被 MAP 激酶途径抑制剂 50 μM PD-98059 和 10 μM SB-203580 抑制。与媒介物处理的对照组相比，腹膜内注射 FGF-23R176Q 24 小时后，注射 FGF-23R176Q 的 C57/B6 小鼠 PGE2 排泄量增加约 10 倍。最后，我们发现 PGE2 抑制体外灌注的小鼠近曲小管中的磷酸盐和体积吸收，并减少体外与 PGE2 孵育的肾皮质中刷状缘膜囊泡 NaPi-2a 蛋白的丰度。总之，FGF-23 通过 MAP 激酶途径增加尿管和肾小管 PGE2 的产生，并且 PGE2 抑制近端小管磷酸盐转运。
Fibroblast growth factor-23 (FGF-23) has been implicated in the renal phosphate wasting in X-linked hypophosphatemia, tumor-induced osteomalacia, and autosomal dominant hypophosphatemic rickets. Recently, we demonstrated thatHypmice have greater urinary PGE2levels compared with C57/B6 mice and that indomethacin administration in vivo and in vitro ameliorates the phosphate transport defect inHypmice. To determine further whether altered prostaglandin metabolism plays a role in the renal phosphate transport defect inHypmice, we incubated renal proximal tubules with arachidonic acid. We find that PGE2production was higher inHypmice than in C57/B6 mice. Incubation of C57/B6 mouse renal proximal tubules with FGF-23R176Q, an active mutant form of FGR23, increased tubular PGE2production, an effect that was inhibited by 50 μM PD-98059 and 10 μM SB-203580, inhibitors of the MAP kinase pathway. C57/B6 mice injected with FGF-23R176Q had a ∼10-fold increase in PGE2excretion 24 h after intraperitoneal injection of FGF-23R176Q compared with vehicle-treated controls. Finally, we show that PGE2inhibited both phosphate and volume absorption in mouse proximal convoluted tubules perfused in vitro and reduced brush-border membrane vesicle NaPi-2a protein abundance from renal cortex incubated in vitro with PGE2. In conclusion, FGF-23 increases urinary and renal tubular PGE2production via the MAP kinase pathway and PGE2inhibits proximal tubule phosphate transport.