Glucocorticoids dexamethasone and prednisolone suppress fibroblast growth factor 23 (FGF23).
Glucocorticoids dexamethasone and prednisolone suppress fibroblast growth factor 23 (FGF23).
复制标题
DOI：
10.1007/s00109-021-02036-8
复制
发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Föller M
中科院分区：
文献类型：
--
作者：
Feger M;Ewendt F;Strotmann J;Schäffler H;Kempe-Teufel D;Glosse P;Stangl GI;Föller M
成纤维细胞生长因子23（FGF23）是一种主要由骨细胞分泌的激素。其最突出的作用是调节肾磷酸盐重吸收和骨化三醇（活性维生素 D，1,25(OH)2D3）的形成，其作用取决于其辅助受体 αKlotho。除了这些作用外，还存在其他旁分泌和内分泌作用。 FGF23 的产生受 1,25(OH)2D3、甲状旁腺激素、膳食磷酸盐摄入量、铁状况以及炎症的调节。糖皮质激素是具有抗炎特性的激素，因此广泛用于治疗急性和慢性炎症性疾病、自身免疫性疾病和恶性肿瘤。本研究探讨糖皮质激素是否影响体外以及小鼠体内 FGF23 的产生。通过半定量实时 PCR 分析 Fgf23 转录。通过ELISA测量FGF23和1,25(OH)2D3的血清浓度。尿磷酸盐和 Ca2+ 排泄量在代谢笼中测定。结果，在 UMR106 大鼠成骨细胞样细胞和 MC3T3-E1 细胞中，地塞米松和泼尼松龙均下调 Fgf23 转录和 FGF23 蛋白合成。 Dexamethasone 增加 UMR106 细胞中 Dmp1 和 Phex（编码 FGF23 调节基因）以及 Nfkbia（编码 NFκB 抑制剂 IκBα）转录。在小鼠中，单次注射地塞米松或泼尼松龙后，12 小时内血清 C 末端和完整 FGF23 浓度以及骨 Fgf23 mRNA 表达显着降低。这些作用与肾磷酸盐排泄增加和 1,25(OH)2D3 形成增强同时发生。我们得出的结论是，单次糖皮质激素治疗会强烈下调 FGF23 血浆浓度。糖皮质激素地塞米松和泼尼松龙在体外抑制骨源性激素成纤维细胞生长因子 23 (FGF23) 的形成。该效应伴随着 UMR106 成骨细胞样细胞中 Dmp1、Phex 和 IκBα（FGF23 的负调节因子）的上调。糖皮质激素受体拮抗剂 RU-486 减弱地塞米松对 FGF23、Dmp1 和 Phex 的作用。在小鼠中，单剂量糖皮质激素可抑制 FGF23 并增强 1,25(OH)2D3（活性维生素 D）。在线版本包含可在 10.1007/s00109-021-02036-8 获取的补充材料。
Fibroblast growth factor 23 (FGF23) is a hormone mainly secreted by bone cells. Its most prominent effects are the regulation of renal phosphate reabsorption and calcitriol (active vitamin D, 1,25(OH)2D3) formation, effects dependent on its co-receptor αKlotho. Besides these actions, further paracrine and endocrine effects exist. The production of FGF23 is regulated by 1,25(OH)2D3, parathyroid hormone, dietary phosphate intake, iron status, as well as inflammation. Glucocorticoids are hormones with anti-inflammatory properties and are, therefore, widely used for acute and chronic inflammatory diseases, autoimmune disorders, and malignancies. The present study explored whether glucocorticoids influence the production of FGF23 in vitro as well as in mice. Fgf23 transcription was analyzed by semi-quantitative real-time PCR. Serum concentrations of FGF23 and 1,25(OH)2D3 were measured by ELISA. Urinary phosphate and Ca2+ excretion were determined in metabolic cages. As a result, in UMR106 rat osteoblast-like cells and in MC3T3-E1 cells, both, dexamethasone and prednisolone, downregulated Fgf23 transcription and FGF23 protein synthesis. Dexamethasone increased Dmp1 and Phex (encoding FGF23-regulating genes) as well as Nfkbia (encoding NFκB inhibitor IκBα) transcription in UMR106 cells. In mice, a single injection of dexamethasone or prednisolone was followed by a significant decrease of serum C-terminal and intact FGF23 concentration and bone Fgf23 mRNA expression within 12 h. These effects were paralleled by increased renal phosphate excretion and enhanced 1,25(OH)2D3 formation. We conclude that a single glucocorticoid treatment strongly downregulates the FGF23 plasma concentration. Glucocorticoids dexamethasone and prednisolone suppress the formation of bone-derived hormone fibroblast growth factor 23 (FGF23) in vitro. The effect is accompanied by an upregulation of Dmp1, Phex, and IκBα, negative regulators of FGF23, in UMR106 osteoblast-like cells. Glucocorticoid receptor antagonist RU-486 attenuates the effect of dexamethasone on FGF23, Dmp1, and Phex. In mice, a single glucocorticoid dose suppresses FGF23 and enhances 1,25(OH)2D3 (active vitamin D). The online version contains supplementary material available at 10.1007/s00109-021-02036-8.
登录
查看更多内容
影响因子：
15.9
作者：
LEVI, M;SHAYMAN, JA;WILSON, P
通讯作者：
WILSON, P
DOI：
10.1073/pnas.1800160115
发表时间：
2018-05-29
影响因子：
11.1
作者：
Baer, Ludmilla;Feger, Martina;Foeller, Michael
通讯作者：
Foeller, Michael
磷酸盐与心血管疾病。
影响因子：
2.9
作者：
Kendrick J;Kestenbaum B;Chonchol M
通讯作者：
Chonchol M
影响因子：
56.9
作者：
AUPHAN, N;DIDONATO, JA;KARIN, M
通讯作者：
KARIN, M
影响因子：
4.6
作者：
Feger M;Hase P;Zhang B;Hirche F;Glosse P;Lang F;Föller M
通讯作者：
Föller M