Homer-Bouthiette C, Xiao L, Hurley Marja M
Yale Internal Medicine Residency Program, Yale New Haven Hospital, New Haven, CT, 06510, USA.
Department of Medicine, School of Medicine, UConn Health, University of Connecticut, 263 Farmington Ave., Farmington, CT, 06030, USA.
Sci Rep. 2021 May 26;11(1):11005. doi: 10.1038/s41598-021-90565-0.
Fibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.
成纤维细胞生长因子2（FGF2）在肌肉骨骼稳态中起重要作用，因此确定了Fgf2减少或敲除对骨骼肌功能和表型的影响。对年轻和年老的野生型（WT）及Fgf2基因敲除（KO）小鼠进行步态分析和肌肉力量测试，结果表明存在与年龄相关的步态障碍和肌肉力量下降，在KO状态下这些情况会加剧。与年轻WT相比，年老WT骨骼肌中的Fgf2 mRNA和蛋白显著减少。与年轻WT相比，年老WT和Fgf2KO的肌纤维横截面积显著减小，纤维化和炎性浸润增加。与年老WT相比，年老Fgf2KO中的炎性细胞进一步显著增加。年老WT和年老Fgf2KO中与脂质相关的基因和肌内脂肪增加，与年老WT相比，年老Fgf2KO中的纤维脂肪细胞进一步增加。在年老WT和年老Fgf2KO中观察到FGF信号受损，包括β-klotho、Fgf21 mRNA、FGF21蛋白、磷酸化FGF受体1和3增加。在年轻和年老的Fgf2KO中，MAPK/ERK1/2显著增加。我们得出结论，Fgf2KO、WT小鼠中与年龄相关的FGF2减少以及在Fgf2表达受损情况下FGF21增加，可能导致小鼠骨骼肌功能受损和肌肉减少症。
