SATELLITE CELLS AND MUSCLE HYPERTROPHY: ROLE OF IGF-I

描述（改编自申请人的摘要）：骨骼肌 响应增加的机械负载的扩大似乎包括 通过生肌过程卫星细胞的增殖和分化 这与这两个时期的增长类型相似但又不同 早期发育和成熟。迄今为止的研究结果表明，胰岛素 生长因子-1 (IGF-1) 以自分泌/旁分泌模式发挥作用， 这些支持肥大的生肌机制的主要介质 成熟骨骼肌纤维的过程。 IGF-1 的潜在机制 调节肌原细胞增殖、分化和 已经使用体外方法描述了融合。前提已提出 关于这些过程是否已识别，人们知之甚少 在体外的条件下，体内的骨骼肌也会发生 由于负荷的慢性增加，肌纤维经历代偿性肥大。 本提案的目的是检验 IGF-1 的假设 通过促进体内生肌过程介导肌肉肥大。的 拟议的实验将采用针对个体骨骼的啮齿动物模型 肌肉。治疗将包括提供生长因子和/或 单独使用抑制剂或与阻力训练联合使用抑制剂 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量化 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.