Leukemia inhibitor factor in skeletal muscle regrowth

在各种医学条件下，在诱导萎缩诱导刺激(即停用)后，促进骨骼肌生长是极其重要的。骨骼肌萎缩可能会增加医疗保健成本，降低生活质量。这项拟议的研究将检验白血病抑制因子(LIF)诱导卫星细胞增殖的机制，以及它在固定10天后肌肉重新生长中可能发挥的作用。这项研究将是新颖的，因为它将确定一种可能的信号机制，该机制可能调节卫星细胞的增殖，并最终影响骨骼肌的生长。此外，这项研究将把一种已知会导致心肌肥大的细胞因子的作用扩展到骨骼肌。这将是一个全新的发现。我收集的实验数据表明，LIF可以通过激活NAK2-STAT2或PI3K通路诱导成肌细胞增殖。此外，我还发现，在后肢制动10天后，经过6天的非卧床恢复，骨骼肌表达了LIF蛋白。因此，有人建议确定哪些信号级联是LIF诱导的卫星增殖所必需的，并确定这一途径是否延伸到整个动物。识别一种细胞因子和一种可能调节肌肉生长的信号机制可能会导致其他对策，最终防止肌肉萎缩。

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.