title: Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle.
abstract: 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.
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Sato
authors.affiliation: Showa University Research Institute for Sport and Exercise Sciences, Yokohama, Japan; Division of Cardiology, Showa University Fujigaoka Rehabilitation Hospital, Yokohama, Japan. Electronic address: yiso@med.showa-u.ac.jp.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Mizukami
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otabe
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasai
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan; Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Showa University Research Institute for Sport and Exercise Sciences, Yokohama, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Sanbe
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Division of Cardiology, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: Cellular senescence; Fibroblast growth factor-23; Mesenchymal stem cell; Skeletal muscle