Impacts of hypoxia and hypoxia-induced factors on skeletal muscle repair and muscle stem cells

缺氧及缺氧诱发因素对骨骼肌修复和肌肉干细胞的影响

• 批准号: 9303877
• 负责人: Hang Yin
• 金额: $ 33万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303877
• 关键词: Aging; American; Binding Sites; Cell Nucleus; Cells; Chronic; Chronic Obstructive Airway Disease; Data; Defect; Disease; Environment; Equilibrium; Exposure to; Gene Expression; Gene Targeting; Genetic; Goals; Growth; Health; Heart failure; Histones; Human; Hypoxia; Hypoxia Inducible Factor; Impairment; In Vitro; Intervention; Knowledge; Life; Light; Locomotion; Maintenance; Mediating; Mediator of activation protein; Metabolism; Molecular; Muscle; Muscle Fibers; Muscle function; Muscle satellite cell; Myopathy; Non-Insulin-Dependent Diabetes Mellitus; Oxygen; Pharmacology; Physiological; Pilot Projects; Play; Population; Process; Public Health; Rest; Role; Signal Transduction; Skeletal Muscle; Stem cells; Therapeutic; Therapeutic Intervention; Translations; Transplantation; Work; cell behavior; genome-wide; human disease; improved; in vitro Model; in vivo; in vivo Model; muscle regeneration; novel strategies; novel therapeutic intervention; postnatal; repaired; response; sarcopenia; satellite cell; self-renewal; skeletal muscle differentiation; skeletal muscle wasting; stem cell niche; tool; transcription factor; transcriptome

PROJECT ABSTRACT   Skeletal muscle plays a pivotal role in locomotion and metabolism. Improper function of skeletal muscle, as seen in conditions such as degenerative myopathies and sarcopenia, has profound impacts on human health. Reversely, many human diseases, such as heart failure, chronic obstructive pulmonary disease and type 2 diabetes, cause impairment of skeletal muscle function. To break the vicious cycle, it is important to understand the molecular mechanisms underlying skeletal muscle repair. Skeletal muscle stem cells (also called satellite cells) serve as an important reservoir of myogenic cells that have the potential to accrete to, repair or even rejuvenate skeletal muscle fibers. The life-long maintenance of this potential relies on orchestrated satellite cell behaviors involving intricate balances between proliferation, differentiation and self- renewal. Accumulating evidence indicate that low oxygen tension (hypoxia) is a physiological stem cell niche factor that regulates stem cell behaviors. However, little is known about the impact of hypoxia and hypoxia- induced signaling on satellite cells and skeletal muscle repair. In the present study, we will 1) identify key factors that mediate the hypoxia signaling in satellite cells; 2) investigate key regulators that modulate satellite cell responses to hypoxia; and 3) explore novel therapeutic approaches that may improve skeletal muscle repair in physiological and human disease-relevant conditions. We expect results from this study will substantially contribute to the understanding of satellite cells and skeletal muscle repair, and also shed light on interventions for improving skeletal muscle health.

项目摘要 -- 骨骼肌在运动和新陈代谢中起着关键作用。骨骼肌功能不正常，如 出现在退行性肌病和骨质疏松症等情况下，对人类健康有深远影响。 相反，许多人类疾病，如心力衰竭、慢性阻塞性肺病和2型 糖尿病，会导致骨骼肌功能受损。要打破恶性循环，重要的是 了解骨骼肌修复的分子机制。骨骼肌干细胞(也 称为卫星细胞)是肌源性细胞的重要储存库，这些细胞有可能附着于， 修复甚至恢复骨骼肌纤维的活力。这种潜力的终生维持依赖于 协调的卫星细胞行为涉及增殖、分化和自我平衡之间的复杂平衡 更新。越来越多的证据表明，低氧压(低氧)是一种生理干细胞生态位 调节干细胞行为的因素。然而，人们对缺氧和缺氧的影响知之甚少。 诱导卫星细胞和骨骼肌修复信号。在本研究中，我们将1)确定关键 调节卫星细胞低氧信号的因素；2)研究调节卫星信号的关键调控因子 细胞对低氧的反应；以及3)探索可能改善骨骼肌的新治疗方法 在生理和人类疾病相关的条件下进行修复。我们预计这项研究的结果将 有助于理解卫星细胞和骨骼肌修复，也有助于阐明 改善骨骼肌健康的干预措施。