SATELLITE CELLS AND MUSCLE HYPERTROPHY: ROLE OF IGF-I

描述（改编自申请人摘要）：骨骼肌 响应于增加的机械载荷的增大似乎包括 通过肌源性过程的卫星细胞增殖和分化 这是类似的，但不同的，在这两个时期看到的增长类型， 早期发育和成熟。迄今为止的研究结果表明，胰岛素样 生长因子-1（IGF-1）以自分泌/旁分泌方式起作用， 这些肌原性机制的主要介质， 在成熟的骨骼肌纤维中的突起。IGF-1的潜在机制 调节肌原性细胞增殖、分化的过程， 已经使用体外方法描述了融合。前提是提出 我们对所发现的过程是否 在体内骨骼肌中也发生， 肌纤维由于负荷的慢性增加而发生代偿性肥大。 本提案的拟议目标是检验IGF-1 通过促进体内肌生成过程介导肌肉肥大。的 拟议中的实验将采用啮齿动物模型， 肌肉.治疗将包括递送生长因子和/或 抑制剂单独或与抗阻训练联合， 目标肌肉。分析将包括形态学，生化，分子， 细胞增殖的显微镜和电子显微镜测量， 分化和融合以及肥大反应的定量 包括肌肉功能的测量。拟议的实验将 阐明IGF-1信号系统在肥大过程中的作用。

DESCRIPTION (Adapted from the applicant's abstract): Skeletal muscle enlargement in response to increased mechanical loading appears to include the proliferation and differentiation of satellite cells via myogenic processes which are similar to, but distinct from, the type of growth seen during both early development and maturation. Findings to date suggest that insulin like growth factor-1 (IGF-1), acting in an autocrine/paracrine mode, serves as a primary mediator of these myogenic mechanisms which support the hypertrophy process in mature skeletal muscle fibers. Potential mechanisms by which IGF-1 modulates the process of myogenic cell proliferation, differentiation, and fusion have been delineated using in vitro approaches. The premise is presented that relatively little is known with regard to whether the processes identified in vitro also occur in skeletal muscle in vivo under conditions in which myofibers undergo compensatory hypertrophy due to chronic increases in loading. The proposed objective of this proposal is to test the hypothesis that IGF-1 mediates muscle hypertrophy by promoting myogenic processes in vivo. The proposed experiments will employ rodent models that target individual skeletal muscles. The treatments will include the delivery of growth factors and / or inhibitory agents either alone or in conjunction with resistance training of the target muscle. Analyses will include morphological, biochemical, molecular, microscopic and electron microscopic measures of cellular proliferation, differentiation and fusion as well as quantification of hypertrophy responses including measurements of muscle function. The proposed experiments will elucidate the role of the IGF-1 signaling system in the hypertrophy process.