雄激素受体在循环机械拉伸下调节肌细胞的分化,其上游和下游信号
Shaoting Fu1, Jing Hu2, Gang Wang2
1School of Exercise and Health, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China; Department of Kinesiology, College of Physical Education, Shanghai Normal University, Shanghai, China.
International journal of biological macromolecules
|October 4, 2024
概括
雄激素受体 (AR) 在肌肉分化中起着关键作用,通过FoxO-MRFs信号传递,通过适度运动 (15%的拉伸) 促进肌肉分化,通过过度运动 (20%的拉伸) 抑制肌肉分化. 阿尔法-7-β-1整合素作为机械刺激和AR活动之间的关键联系.
科学领域:
- 肌肉生理学和细胞生物学
- 机械传导的分子机制.
- 在肌肉发育中的雄激素受体信号传递.
背景情况:
- 雄激素受体 (AR) 在机械拉伸下对肌细胞增殖至关重要.
- AR在肌肉细胞分化中的作用及其调节途径在很大程度上是未知的.
- 了解AR在分化中的功能对于肌肉质量和力量调节至关重要.
研究的目的:
- 在机械拉伸下,比较AR表达 (C2C12) 和非表达 (L6) 核细胞之间的肌体差异化.
- 阐明AR在拉伸调节肌细胞分化中的作用,使用激动剂和抗剂.
- 在机械拉伸过程中识别AR的上游和下游信号分子.
主要方法:
- 在15%和20%的机械拉伸下对肌细胞分化 (C2C12与L6) 的比较分析.
- 使用花胺 (对抗剂) 和GTx-007 (激动剂) 对AR活性进行药理学操纵.
- RNA测序 (RNA-seq),分子动态模拟 (MD) 和共同免疫沉以识别信号通路和相互作用蛋白质.
主要成果:
- 15%的拉伸增强,而20%的拉伸抑制,肌管形成,在C2C12细胞中产生更大的影响.
- AR调节证实了它的作用:花胺阻断了15%的拉伸诱导差异化,GTx-007逆转了20%的拉伸诱导抑制.
- RNA-seq显示了FoxO,JAK-STAT和MAPK通路的丰富;MD和co-IP确定了β1整蛋白作为AR相互作用伙伴.
结论:
- AR对于介导机械拉伸对神经细胞分化的影响至关重要,在15%的拉伸中促进它,在20%的拉伸中抑制它.
- 福克斯-MRFs通路是AR在拉伸调节差异化中的作用的核心.
- 阿尔法-7-β-1整合素作为机械传感器,将机械刺激与细胞内AR信号联系起来.
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