Leukemia inhibitor factor in skeletal muscle regrowth

骨骼肌再生中的白血病抑制因子

• 批准号: 6445216
• 负责人: ESPEN E SPANGENBURG
• 金额: $ 3.78万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-08 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6445216
• 关键词: atrophy; biological signal transduction; cell proliferation; immobilization of body part; immunoprecipitation; laboratory rat; leg; leukemia inhibitory factor; muscle satellite cell; phosphatidylinositol 3 kinase; regeneration; striated muscles; tissue /cell culture

Increasing skeletal muscle growth after an induction of an atrophying inducing stimulus (i.e. disuse) is extremely important in various medical conditions. Skeletal muscle wasting can contribute to increased health care costs and a decreased quality of life. The proposed research would examine the mechanism that allows Leukemia Inhibitory Factor (LIF) to inducer satellite cell proliferation and the role it may play in muscle re- growth after 10 days of immobilization. This research would be novel in that it would identify a possible signaling mechanism that may regulate satellite cell proliferation and ultimately affect skeletal muscle growth. Further, the research would extend the role of a cytokine known to cause cardiac hypertrophy to skeletal muscle. This would be a completely novel finding. Pilot data that I have colleted indicates that LIF can induce myoblast proliferation, possibly by activating the NAK2-STAT2 or PI3K pathways. Also, I found that skeletal muscle expressed the LIF protein after 6 days of ambulatory recovery from 10 days of hindlimb immobilization. Therefore, it is proposed to determine which signaling cascades are necessary for LIF-indued satellite proliferation and to determine if this pathway extends to the whole animal. Identification of a cytokine and a signaling mechanism that may regulate muscle growth could lead to other counter-measures to ultimately prevent muscle wasting.

诱导萎缩刺激（即废弃）后，骨骼肌生长的增加在各种医疗状况中非常重要。骨骼肌浪费会导致医疗保健成本增加和生活质量下降。拟议的研究将检查允许白血病抑制因子（LIF）诱导卫星细胞增殖及其在固定10天后在肌肉增长中起作用的机制。这项研究将是新颖的，因为它将确定可能调节卫星细胞增殖并最终影响骨骼肌生长的可能信号传导机制。此外，这项研究将扩大已知会导致心脏肥大到骨骼肌的细胞因子的作用。这将是一个完全新颖的发现。我已填充的试点数据表明，LIF可以通过激活NAK2-STAT2或PI3K途径来诱导肌细胞增殖。另外，我发现骨骼肌从固定后的10天内门诊恢复了6天后表达了LIF蛋白。 因此，建议确定哪些信号级联对于LIF指定的卫星增殖是必需的，并确定该途径是否延伸到整个动物。鉴定细胞因子和可能调节肌肉生长的信号传导机制可能会导致其他反措施，以最终防止肌肉浪费。