Klotho 对 UMR-106 成骨样细胞中纤维母细胞生长因子 23 合成的抑制作用。
The suppressive effect of soluble Klotho on fibroblastic growth factor 23 synthesis in UMR-106 osteoblast-like cells.
机构信息
Department of Nephrology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
出版信息
Cell Biol Int. 2018 Sep;42(9):1270-1274. doi: 10.1002/cbin.10997. Epub 2018 Jun 15.
Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (i) control group; (ii) β-glycerophosphate (β-GP) group; (iii) β-GP + Klotho group; (iv) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (v) β-GP + Klotho + LiCl group. Subsequently, UMR-106 cells were cultured for 72 h, and the expression of FGF23, P-glycogen synthase kinase-3β (P-GSK-3β), and glycogen synthase kinase-3β(GSK-3β) were measured with Western blot analysis. The mRNA levels of FGF23 and the Wnt/β-catenin pathway target gene c-myc were determined with RT-qPCR. The results showed that β-GP induced increased expression of FGF23 mRNA and protein. Compared with the β-GP group, expression of FGF23 mRNA and protein expression were downregulated in the β-GP + Klotho group. In addition, β-GP induced increased expression of P-GSK-3β/GSK-3β and c-myc, which were all downregulated in the β-GP + Klotho group. Moreover, the expression of FGF23, P-GSK-3β/GSK-3β, and c-myc mRNA were upregulated when treated with LiCl. These results demonstrate that soluble Klotho suppresses FGF23 synthesis in osteoblast-like UMR-106 cells. The mechanism of this suppression may be partially through the inhibition of the Wnt/β-catenin pathway.
成纤维细胞生长因子 23（FGF23）主要由骨骼分泌。慢性肾脏病（CKD）患者血清中 FGF23 升高，但确切机制尚不清楚。Klotho 被鉴定为衰老抑制剂，主要在肾脏表达，CKD 患者可溶性 Klotho 与 FGF23 呈负相关。本研究旨在探讨 Klotho 对成骨样 UMR-106 细胞 FGF23 合成的影响及其可能机制。将 UMR-106 细胞分为五组：（i）对照组；（ii）β-甘油磷酸（β-GP）组；（iii）β-GP+Klotho 组；（iv）β-GP+氯化锂（LiCl，Wnt/β-catenin 通路激动剂）组；和（v）β-GP+Klotho+LiCl 组。随后，将 UMR-106 细胞培养 72 小时，用 Western blot 分析测定 FGF23、P-糖原合酶激酶-3β（P-GSK-3β）和糖原合酶激酶-3β（GSK-3β）的表达。用 RT-qPCR 测定 FGF23 和 Wnt/β-catenin 通路靶基因 c-myc 的 mRNA 水平。结果表明，β-GP 诱导 FGF23 mRNA 和蛋白表达增加。与β-GP 组相比，β-GP+Klotho 组 FGF23 mRNA 和蛋白表达下调。此外，β-GP 诱导 P-GSK-3β/GSK-3β 和 c-myc 表达增加，而在β-GP+Klotho 组均下调。此外，用 LiCl 处理时，FGF23、P-GSK-3β/GSK-3β 和 c-myc mRNA 的表达上调。这些结果表明，可溶性 Klotho 抑制成骨样 UMR-106 细胞中 FGF23 的合成。这种抑制的机制可能部分通过抑制 Wnt/β-catenin 通路。
Zotero 插件