Fibroblast Growth Factor 23 Expression Is Increased in Multiple Organs in Mice With Folic Acid-Induced Acute Kidney Injury.
Fibroblast Growth Factor 23 Expression Is Increased in Multiple Organs in Mice With Folic Acid-Induced Acute Kidney Injury.
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DOI：
10.3389/fphys.2018.01494
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发表时间：
2018
影响因子：
4
通讯作者：
Perwad F
中科院分区：
文献类型：
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作者：
Egli-Spichtig D;Zhang MYH;Perwad F
成纤维细胞生长因子23（FGF 23）调节磷酸盐稳态和维生素D代谢。在急性肾损伤（阿基）患者中，FGF 23水平在阿基发作后迅速升高，并与阿基进展和死亡率增加相关。在阿基小鼠模型中，FGF 23水平的过度升高伴随着骨骼中FGF 23表达的适度增加。我们检查了叶酸诱导的阿基（FA-AKI）小鼠模型，以确定其他器官是否有助于血浆FGF 23的增加，并评估了维生素D轴作为FGF 23基因表达增加的可能触发因素。FA-AKI开始后24小时，血浆完整FGF 23和1，25（OH）2D增加，肾功能下降。FA处理的小鼠发生肾脏炎症，如通过增加的Tnf和Tgfb mRNA表达所示。Fgf 23 mRNA表达在FA处理小鼠的胸腺、脾脏和心脏中分别上调5- 15倍，但在骨中仅上调2倍。在FA-AKI小鼠中还检测到异位肾Fgf 23 mRNA表达。血浆FGF 23和Fgf 23 mRNA在胸腺、脾脏、心脏和骨骼中的表达与肾脏TNF mRNA的表达密切相关。此外，Vdr mRNA的表达上调，在脾脏，胸腺和心脏，并强烈相关的Fgf 23 mRNA的表达在同一器官。总之，FA-AKI小鼠中血浆FGF 23的快速升高伴随着多个器官中Fgf 23 mRNA表达的增加和骨外组织中Vdr表达的增加以及血浆1，25（OH）2D的增加，并且炎症可能触发FA-AKI中FGF 23的升高。
Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and vitamin D metabolism. In patients with acute kidney injury (AKI), FGF23 levels rise rapidly after onset of AKI and are associated with AKI progression and increased mortality. In mouse models of AKI, excessive rise in FGF23 levels is accompanied by a moderate increase in FGF23 expression in bone. We examined the folic acid-induced AKI (FA-AKI) mouse model to determine whether other organs contribute to the increase in plasma FGF23 and assessed the vitamin D axis as a possible trigger for increased Fgf23 gene expression. Twenty-four hours after initiation of FA-AKI, plasma intact FGF23 and 1,25(OH)2D were increased and kidney function declined. FA-treated mice developed renal inflammation as shown by increased Tnf and Tgfb mRNA expression. Fgf23 mRNA expression was 5- to 15-fold upregulated in thymus, spleen and heart of FA-treated mice, respectively, but only 2-fold in bone. Ectopic renal Fgf23 mRNA expression was also detected in FA-AKI mice. Plasma FGF23 and Fgf23 mRNA expression in thymus, spleen, heart, and bone strongly correlated with renal Tnf mRNA expression. Furthermore, Vdr mRNA expression was upregulated in spleen, thymus and heart and strongly correlated with Fgf23 mRNA expression in the same organ. In conclusion, the rapid rise in plasma FGF23 in FA-AKI mice is accompanied by increased Fgf23 mRNA expression in multiple organs and increased Vdr expression in extra osseous tissues together with increased plasma 1,25(OH)2D and inflammation may trigger the rise in FGF23 in FA-AKI.