Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle

• Published in: Biochemical and biophysical research communications Vol. 470; no. 3; pp. 657 - 662
• Main Authors: Sato, Chisato, Iso, Yoshitaka, Mizukami, Takuya, Otabe, Koji, Sasai, Masahiro, Kurata, Masaaki, Sanbe, Takeyuki, Sekiya, Ichiro, Miyazaki, Akira, Suzuki, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.02.2016
• Subjects: angiotensin II; beta-galactosidase; Cell Differentiation - physiology; cell senescence; Cells, Cultured; Cellular senescence; Cellular Senescence - physiology; fibroblast growth factor receptors; Fibroblast growth factor-23; Fibroblast Growth Factors - metabolism; fibroblasts; gene expression; genes; homeostasis; Humans; kidney diseases; Mesenchymal stem cell; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; muscles; oxidative stress; patients; phenotype; Skeletal muscle; stem cells; Western blotting; Mesenchymal stem cell; Fibroblast growth factor-23; Skeletal muscle; Cellular senescence
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.01.086

Although muscle wasting and/or degeneration are prevalent in patients with chronic kidney disease, it remains unknown whether FGF-23 influences muscle homeostasis and regeneration. Mesenchymal stem cells (MSCs) in skeletal muscle are distinct from satellite cells and have a known association with muscle degeneration. In this study we sought to investigate the effects of FGF-23 on MSCs isolated from human skeletal muscle in vitro. The MSCs expressed FGF receptors (1 through 4) and angiotensin-II type 1 receptor, but no traces of the Klotho gene were detected. MSCs and satellite cells were treated with FGF-23 and angiotensin-II for 48 h. Treatment with FGF-23 significantly decreased the number of MSCs compared to controls, while treatment with angiotensin-II did not. FGF-23 and angiotensin-II both left the cell counts of the satellite cells unchanged. The FGF-23-treated MSCs exhibited the senescent phenotype, as judged by senescence-associated β-galactosidase assay, cell morphology, and increased expression of p53 and p21 in western blot analysis. FGF-23 also significantly altered the gene expression of oxidative stress regulators in the cells. In conclusion, FGF-23 induced premature senescence in MSCs from skeletal muscle via the p53/p21/oxidative-stress pathway. The interaction between the MSCs and FGF-23 may play a key role in the impaired muscle reparative mechanisms of chronic kidney disease. •Human MSCs from skeletal muscle expressed FGF receptors but not Klotho.•FGF-23 decreased the MSC number and increased senescent phenotype of the cells.•FGF-23 induced premature senescence in the MSCs via the p53/p21/oxidative-stress pathway.