Roles of intracellular signaling molecules in the processes of neuromuscular system reconstitution

细胞内信号分子在神经肌肉系统重建过程中的作用

• 批准号: 13670030
• 负责人: KAMI Katsuya
• 金额: $ 2.11万
• 依托单位: Osaka University of Health and Sport Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670030/
• 关键词: Skeletal muscle regeneration; cytokine; muscle satellite cell; myotube; LIF; STAT3; proliferation; differentiation; サテライト細胞; 運動ニューロン; in situハイブリダイゼーション; 免疫組織化学; MyoD; PCNA; 細胞内シグナル伝達分子; 筋前駆体細胞; 免疫組織化学法

Although growth factors and cytokines play critical roles in skeletal muscle regeneration, intracellular signaling molecules that are activated by these factors in regenerating muscles have been not elucidated. Several lines of evidence suggest that leukemia inhibitory factor (LIF) is an important cytokine for the proliferation and survival of myoblasts in vitro and acceleration of skeletal muscle regeneration. To elucidate the role of LIF signaling in regenerative responses of skeletal muscles, we examined the spatial and temporal activation patterns of a LIF-associated signaling molecule, the signal transducer and activator of transcription 3 (STAT3) proteins in regenerating rat skeletal muscles induced by crush injury. At the early stage of regeneration, activated STAT3 proteins were first detected in c-Met-positive activated satellite cell nuclei, and then continued to be activated in proliferating myoblasts expressing both PCNA and MyoD proteins. When muscle regeneration progressed, STAT3 signaling was no longer activated in differentiated myoblasts and myotubes. In addition, activation of STAT3 was also detected in myonuclei located within intact sarcolemmas of surviving myofibers which did not show signs of necrosis. These findings suggest that activation of STAT3 signaling is an important molecular event which induces the successful regeneration of injured skeletal muscles.

尽管生长因子和细胞因子在骨骼肌再生中发挥着关键作用，但在肌肉再生过程中被这些因子激活的细胞内信号分子尚未阐明。多项证据表明，白血病抑制因子 (LIF) 是体外成肌细胞增殖和存活以及加速骨骼肌再生的重要细胞因子。为了阐明 LIF 信号在骨骼肌再生反应中的作用，我们检查了 LIF 相关信号分子、信号转导器和转录激活剂 3 (STAT3) 蛋白在挤压诱导的大鼠骨骼肌再生中的空间和时间激活模式。受伤。在再生早期，激活的STAT3蛋白首先在c-Met阳性激活的卫星细胞核中检测到，然后在表达PCNA和MyoD蛋白的增殖成肌细胞中继续被激活。当肌肉再生进展时，STAT3 信号在分化的成肌细胞和肌管中不再激活。此外，在未表现出坏死迹象的存活肌纤维的完整肌膜内的肌核中也检测到了 STAT3 的激活。这些发现表明 STAT3 信号传导的激活是诱导受损骨骼肌成功再生的重要分子事件。

项目成果

上 勝也, 仙波 恵美子: "筋再生と細胞内シグナル伝達"生体の科学. 第52巻. 328-333 (2001)

Katsuya Kami、Emiko Senba：“肌肉再生和细胞内信号转导”生物科学卷 52. 328-333 (2001)。

上 勝也: "新運動生理学(下巻)"真興交易(株)医学出版部. 15 (2001)

加美克也：《新运动生理学（第2卷）》新光贸易株式会社医学出版部15（2001年）。

上 勝也: "筋再生と細胞内シグナル伝達"生体の科学. 52巻. 328-333 (2001)

Katsuya Kami：“肌肉再生和细胞内信号转导”生物科学卷 52. 328-333 (2001)。

上 勝也: "骨格筋の適応変化-細胞・分子レベルでの観察-"バイオメカニクス研究. 第6巻. 208-219 (2002)

Katsuya Kami：“骨骼肌的适应性变化 - 细胞和分子水平的观察”生物力学研究，第 6 卷，208-219（2002 年）。

Kami K, Senba E: "In vivo activation of STAT3 signaling in satellite cells and myofibers in regenerating skeletal muscles"J Histochem Cytochem. Vol.50. 1579-1589 (2002)

Kami K、Senba E：“再生骨骼肌中卫星细胞和肌纤维中 STAT3 信号的体内激活”J Histochem Cytochem。