Adipogenic vs Myogenic Signaling in Muscle Regeneration

肌肉再生中的成脂与肌源信号传导

• 批准号: 6937570
• 负责人: Veronica E Contreras-Shannon
• 金额: $ 2.84万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937570
• 关键词: adipocytes; biological signal transduction; cell differentiation; laboratory mouse; muscle satellite cell; musculoskeletal regeneration; myogenesis; peroxisome proliferator activated receptor; postdoctoral investigator; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): A population of normally quiescent satellite cells that reside adjacent to skeletal muscle fibers is responsible for muscle regeneration following injury. Activation of these satellite cells and the regeneration of damaged muscle may be dependent on macrophage infiltration. Preliminary studies of mice with altered inflammation demonstrated delays in muscle regeneration and increased adiposity within muscle following injury. Increased fat deposition within and between skeletal muscle fibers also occurs in aging due to impairments in muscle regeneration. Factors present in the healing microenvironment during injury and altered inflammation may direct the differentiation fate of satellite cells to adipocyte rather than muscle by shifting the expression of specific transcription factors. The proposed studies will determine the contribution of the healing microenvironment and transcriptional signaling events that direct adipogenic rather than myogenic differentiation of satellite cells. The specific aims are to: 1) determine the expression levels of myogenic and adipogenic transcription factors to uncover changes in transcriptional events leading to the altered muscle regeneration observed in CCR2 -/- mice following injury, 2) verify that the healing microenvironment contributes to altered muscle regeneration using in vitro satellite cell culture and 3) demonstrate that conditions which favor the upregulation of adipogenic vs myogenic transcription factors promote an adipogenic or myogenic phenotype, respectively, in regenerating muscle.

描述（由申请人提供）：位于骨骼肌纤维附近的一群通常静止的卫星细胞负责损伤后的肌肉再生。这些卫星细胞的激活和受损肌肉的再生可能依赖于巨噬细胞浸润。对炎症改变的小鼠的初步研究表明，损伤后肌肉再生延迟，肌肉内脂肪增多。骨骼肌纤维内和之间的脂肪沉积增加也发生在由于肌肉再生障碍的衰老中。在损伤和炎症改变过程中，愈合微环境中存在的因素可能通过改变特定转录因子的表达，将卫星细胞的分化命运引导为脂肪细胞而不是肌肉。拟议的研究将确定愈合微环境和转录信号事件的贡献，直接成脂而不是成肌分化的卫星细胞。具体目标是：1）确定成肌和成脂转录因子的表达水平以揭示导致损伤后在CCR 2-/-小鼠中观察到的改变的肌肉再生的转录事件的变化，2）使用体外卫星细胞培养验证愈合微环境有助于改变肌肉再生，以及3）证明了有利于脂肪生成转录因子与肌生成转录因子上调的条件分别促进再生肌肉中的脂肪生成或肌生成表型。