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首页> 外文期刊>Molecular and Cellular Biology >Reduced Mobility of Fibroblast Growth Factor (FGF)-Deficient Myoblasts Might Contribute to Dystrophic Changes in the Musculature of FGF2/FGF6/mdx Triple-Mutant Mice
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Reduced Mobility of Fibroblast Growth Factor (FGF)-Deficient Myoblasts Might Contribute to Dystrophic Changes in the Musculature of FGF2/FGF6/mdx Triple-Mutant Mice

机译：成纤维细胞生长因子（FGF）缺乏成肌细胞的减少的移动可能有助于FGF2 / FGF6 / mdx三重突变小鼠的肌肉营养不良性变化。

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Development and regeneration of muscle tissue is a highly organized, multistep process that requires cell proliferation, migration, differentiation, and maturation. Previous data implicate fibroblast growth factors (FGFs) as critical regulators of these processes, although their precise role in vivo is still not clear. We have explored the consequences of the loss of multiple FGFs (FGF2 and FGF6 in particular) for muscle regeneration in mdx mice, which serve as a model for chronic muscle damage. We show that the combined loss of FGF2 and FGF6 leads to severe dystrophic changes in the musculature. We found that FGF6 mutant myoblasts had decreased migration ability in vivo, whereas wild-type myoblasts migrated normally in a FGF6 mutant environment after transplantation of genetically labeled myoblasts from FGF6 mutants in wild-type mice and vice versa. In addition, retrovirus-mediated expression of dominant-negative versions of Ras and Ral led to a reduced migration of transplanted myoblasts in vivo. We propose that FGFs are critical components of the muscle regeneration machinery that enhance skeletal muscle regeneration, probably by stimulation of muscle stem cell migration.
机译：肌肉组织的发育和再生是一个高度组织的多步骤过程，需要细胞增殖，迁移，分化和成熟。尽管尚不清楚它们在体内的确切作用，但先前的数据暗示成纤维细胞生长因子（FGFs）是这些过程的关键调节因子。我们已经探索了多种FGF（特别是FGF2和FGF6）的损失对mdx小鼠肌肉再生的影响，mdx小鼠可作为慢性肌肉损伤的模型。我们表明FGF2和FGF6的联合损失导致肌肉系统严重营养不良的变化。我们发现，FGF6突变成肌细胞在体内的迁移能力降低，而野生型成肌细胞在从FGF6突变体遗传标记的成肌细胞移植到野生型小鼠后，在FGF6突变体环境中正常迁移，反之亦然。此外，逆转录病毒介导的Ras和Ral显性阴性版本的表达导致体内移植的成肌细胞迁移减少。我们认为，FGFs是可能通过刺激肌肉干细胞迁移而增强骨骼肌再生的肌肉再生机制的关键组成部分。

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