The role of p107 in skeletal muscle adaption: Understanding progenitor cell differentiation into muscle fiber

p107 在骨骼肌适应中的作用：了解祖细胞分化为肌纤维

• 批准号: 402397-2012
• 负责人: Scime, Anthony
• 金额: $ 1.82万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573272
• 关键词: role; p107; skeletal; muscle; adaption

The fiber characteristics in skeletal muscle control how the muscle will function. In the mouse, used as a model for human physiology, the muscle fiber types are generally classified according to four major forms. These forms display differences with respect to their metabolic potential, i.e. how much and what type of food energy will be consumed. The fibers consist of slow oxidative types, that are the primary muscle type of an endurance athlete and fast glycolytic types that are the predominate muscle type of athletes using quick bursts of energy, such as sprinters. In response to physiological pressures such as exercise and diet, adult skeletal muscle can switch fiber types. Currently, it is not known how the muscle stem cells lead to specific fiber types. Our research program is involved in finding how and why the muscle stem cells become determined to a fast or slow fiber type fate. Our recent published results show that a protein called p107 plays a role in determining the fiber type character of skeletal muscle. We had demonstrated that mice that do not possess p107 have higher levels of slow type muscle fibers. Our results therefore indicate a central role for p107 in determining the metabolic state of skeletal muscle by controlling what fiber types will be made. Our research program addresses how p107 controls the stem cells to produce the fast fiber types over the slower ones. This will be accomplished by three different approaches. 1) We will determine the molecular role of p107 in muscle fiber type commitment, 2) We will discover the p107 interacting partners during fiber type formation and 3) we will find how p107 behaves during exercise. Our research will provide important insight into how p107 controls stem cells to make specific fiber types.

骨骼肌中的纤维特性控制着肌肉的功能。在小鼠中，用作人体生理学的模型，肌纤维类型通常根据四种主要形式分类。这些形式在其代谢潜力方面表现出差异，即消耗多少和什么类型的食物能量。这些纤维由慢氧化型和快速糖酵解型组成，慢氧化型是耐力运动员的主要肌肉类型，而快速糖酵解型是使用快速爆发能量的运动员（如短跑运动员）的主要肌肉类型。为了应对运动和饮食等生理压力，成人骨骼肌可以转换纤维类型。目前，尚不清楚肌肉干细胞如何导致特定的纤维类型。我们的研究计划涉及发现肌肉干细胞如何以及为什么决定快速或缓慢的纤维类型命运。我们最近发表的研究结果表明，一种名为p107的蛋白质在决定骨骼肌的纤维类型特征中起着重要作用。我们已经证明，不具有p107的小鼠具有更高水平的慢型肌纤维。因此，我们的研究结果表明，p107在决定骨骼肌的代谢状态，通过控制什么样的纤维类型将作出核心作用。我们的研究计划解决了p107如何控制干细胞产生快速纤维类型而不是慢速纤维类型。这将通过三种不同的方法来实现。1)我们将确定p107在肌纤维类型定型中的分子作用，2）我们将发现p107在纤维类型形成过程中的相互作用伙伴，3）我们将发现p107在运动过程中的行为。我们的研究将为p107如何控制干细胞制造特定的纤维类型提供重要的见解。