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Relationships between ultrastructural profiles and signal transduction of bone and skeletal muscle cells following development and growth

发育和生长后骨和骨骼肌细胞的超微结构特征与信号转导之间的关系

基本信息

批准号：
13480010
负责人：
KURATA Hiroshi
金额：
$ 9.98万
依托单位：
National Institute of Fitness and Sports in Kanoya
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Although growth factors and cytokines play significant roles in skeletal muscle regeneration, intracellular signaling molecules that are activated these factors in regenerating muscle cells have been not elucidated.Several lines of evidence suggest that leukemia inhibitory factor(LIF)is an important cytokines for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle cell regeneration.MyoD, myogenin, proliferating cell nuclear antigen(PCNA)and cyclin-dependent kinase inhibitor p21(p21)proteins are also key molecules in inducing the growth of muscle cells in vitro.To elucidate the role of these factors signaling in regenerative responses of skeletal muscle cells, we examined the spatial and temporal activation patterns of these signaling molecules in regenerating and in functionally overloaded rat skeletal muscle cells using immunohistochemical procedures.MyoD and myogenin were detected in myonuclei located inside the dystrophin-positive plasma membrane of myofibers, m-cadherin-positive satellite cell nuclei and nuclei located in the interstitial spaces between myofibers.At the early stage of regeneration, activated STAT3 proteins were first detected in the nuclei of activated satellite cells and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins.When muscle cell regeneration processed, the signal transducer and activator transcription 3(STAT3)proteins was no longer activated in differentiated myoblasts and myotubes.In addition, activation of STAT3 was also detected in myonuclei within intact sarcolemmas of surviving myofibers that did not show signs of necrosis.Activation of STAT3 signaling is an important molecular event that induces the successful regeneration of skeletal muscle cells.And continual expression of MyoD and myogenin proteins in these cells is an essential molecular event which induces the successful hypertrophy of skeletal muscle cells.

尽管生长因子和细胞因子在骨骼肌再生中起着重要的作用，但激活这些因子的细胞内信号分子在再生肌肉细胞中的作用尚未阐明。一些证据表明，白血病抑制因子(LIF)是体外培养成肌细胞增殖和存活以及加速骨骼肌细胞再生的重要细胞因子。MyoD、肌生成素、增殖细胞核抗原(PCNA)和细胞周期蛋白依赖性激酶抑制因子p21(P21)蛋白也是诱导体外培养的肌肉细胞生长的关键分子。为了阐明这些因子信号在骨骼肌细胞再生反应中的作用，我们用免疫组织化学方法研究了这些信号分子在再生和功能超负荷的大鼠骨骼肌细胞中的时空激活模式。在肌纤维的dystrophin阳性质膜内的肌核、m-cadherin阳性的卫星细胞核和位于肌纤维间隙的核中检测到MyoD和mygenin。此外，在再生的早期阶段，激活的STAT3蛋白首先在激活的卫星细胞的核中检测到，然后在表达增殖的成肌细胞中继续激活。当肌肉细胞再生时，信号转导和激活因子转录3(STAT3)蛋白在分化的肌母细胞和肌管中不再被激活STAT3信号通路的激活是诱导骨骼肌细胞成功再生的重要分子事件，而MyoD和mygenin蛋白在这些细胞中的持续表达是导致骨骼肌细胞成功肥大的重要分子事件。