Stretch Mediated Myoblast Proliferation and/or Survival

描述（由申请人提供）：骨骼肌的生长与肌母细胞与肌管融合后新形成的细胞核的增加有关，并依赖于此。因此，肌纤维的生长能力严重依赖于成肌细胞的增殖和/或存活。循环机械拉伸刺激多种细胞类型的增殖（9,15）。因此，我们将利用培养成肌细胞的循环机械拉伸来识别可能调节成肌细胞增殖和/或存活的信号转导途径。该方案有三个总体目标：(1)确定拉伸对成肌细胞增殖和/或存活的影响；(2)确定钙调神经磷酸酶（CaN）及其下游效应物活化T细胞核因子（NFAT）在调节周期性机械拉伸后成肌细胞增殖和/或存活中的作用；(3)阐明血管内皮生长因子（VEGF）在周期性机械拉伸后成肌细胞增殖和/或存活中的潜在作用。了解调节肌肉生长的分子机制对于开发有效的药物或基因疗法来对抗与肌肉萎缩相关的临床疾病非常重要。

DESCRIPTION (provided by applicant): Skeletal muscle growth is associated with, and dependent upon, the addition of newly formed nuclei via the fusion of myoblasts to the myotube. Thus, the capability of muscle fibers to grow is critically dependent on myoblast proliferation and/or survival. Cyclic mechanical stretch stimulates proliferation in a variety of cell types (9, 15). Therefore, we will utilize cyclic mechanical stretch of cultured myoblasts to identify signal transduction pathways that potentially regulate myoblast proliferation and/or survival. This proposal has three overall goals: (1) to determine the influence of stretch on myoblast proliferation and/or survival; (2) to identify the role of calcineurin (CaN) and its downstream effector Nuclear Factor of Activated T Cells (NFAT) in regulating myoblast proliferation and/or survival secondary to cyclic mechanical stretch; and, (3) to elucidate a potential role for Vascular Endothelial Growth Factor (VEGF) on myoblast proliferation and/or survival following cyclic mechanical stretch. Understanding the molecular mechanisms that regulate muscle growth is important for developing effective pharmacologic or genetic therapies to combat the number of clinical conditions associated with muscle atrophy.