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The suppressive effect of soluble Klotho on fibroblastic growth factor 23 synthesis in UMR‐106 osteoblast‐like cells
Author(s) -
Ma Lulu,
Gao Min,
Wu Lin,
Zhao Xiufen,
Mao Huijuan,
Xing Changying
Publication year - 2018
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10997
Subject(s) - klotho , gsk 3 , endocrinology , medicine , fibroblast growth factor 23 , glycogen synthase , wnt signaling pathway , downregulation and upregulation , gsk3b , chemistry , osteoblast , kinase , biology , signal transduction , kidney , parathyroid hormone , glycogen , biochemistry , gene , calcium , in vitro
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.