The role of the Rb family in skeletal muscle adaptation

Rb 家族在骨骼肌适应中的作用

• 批准号: RGPIN-2018-05937
• 负责人: Scime, Anthony
• 金额: $ 2.11万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757090
• 关键词: role; Rb; family; skeletal; muscle

The role of the Rb family in skeletal muscle adaptationMetabolism is the chemical processes occurring within an organism that is necessary for the maintenance of life. Our research program is to understand the novel role of the retinoblastoma susceptibility (Rb) family (Rb, p107 and p130) of transcriptional repressor proteins in regulating metabolism. To date, very little is known for how and why they function in controlling the metabolism of cells. Our short-term goal outlined in this proposal is to examine their role in skeletal muscle metabolism. Skeletal muscle is a highly plastic tissue with the ability to undergo functional changes, including their metabolic state. These adaptive changes occur within the muscle fibers and their stem cells. We will address molecular, cellular and physiological roles of the Rb family in skeletal muscle metabolic adaptations by the following 3 objectives:1. To discover a metabolic role for how the Rb family influences muscle fiber formation. Muscle fiber type changes are a read-out for the metabolic state of the skeletal muscle. The function of the Rb family during stem cell differentiation into fiber types will be characterized. Using this strategy, we expect to find a metabolic role for the Rb family during muscle fiber formation. 2. To understand Rb family-mediated metabolic adaptation in muscle under physiologic stress. Specifically, we will determine how the Rb family members are involved in facilitating muscle metabolic changes associated with exercise and diet. This will allow us to find how stress influences stem cell function and skeletal muscle fiber changes in the context of the Rb family members.3. To determine the influence of the muscle microenvironment on the Rb family and muscle metabolic adaptation. We will determine the effect of nutrients and metabolic inhibitors on the Rb family members in muscle stem cells and fiber changes using isolated muscle fibers. This will provide knowledge about how nutritional and metabolic pathways affects the Rb family in the context of the muscle microenvironment. Our results will highlight a new role of influencing metabolism for the Rb family. This insight will benefit the scientific community by providing innovative information about how muscle metabolic changes occur.

Rb家族在骨骼肌适应中的作用代谢是生物体内发生的维持生命所必需的化学过程。我们的研究计划是了解视网膜母细胞瘤易感性（Rb）家族（Rb，p107和p130）的转录抑制蛋白在调节代谢中的新作用。迄今为止，很少有人知道它们如何以及为什么在控制细胞代谢中发挥作用。我们的短期目标概述了这一建议是检查他们在骨骼肌代谢中的作用。骨骼肌是一种高度可塑性的组织，具有进行功能变化的能力，包括其代谢状态。这些适应性变化发生在肌肉纤维及其干细胞中。本论文主要从以下三个方面阐述Rb家族在骨骼肌代谢适应中的分子、细胞和生理作用：1.发现Rb家族如何影响肌纤维形成的代谢作用。肌纤维类型变化是骨骼肌代谢状态的读数。Rb家族在干细胞分化成纤维类型过程中的功能将被表征。使用这种策略，我们希望找到Rb家族在肌纤维形成过程中的代谢作用。2.了解生理应激下Rb家族介导的肌肉代谢适应。具体来说，我们将确定Rb家族成员如何参与促进与运动和饮食相关的肌肉代谢变化。这将使我们能够发现压力如何影响Rb家族成员背景下的干细胞功能和骨骼肌纤维变化。研究肌肉微环境对Rb家族和肌肉代谢适应的影响。我们将确定营养素和代谢抑制剂对肌肉干细胞中Rb家族成员的影响，并使用分离的肌纤维进行纤维变化。这将提供有关营养和代谢途径如何在肌肉微环境中影响Rb家族的知识。我们的研究结果将突出Rb家族影响代谢的新作用。这一见解将通过提供有关肌肉代谢变化如何发生的创新信息而使科学界受益。