限制受伤诱导的脂肪生成
Daniel Kopinke1, Elle C Roberson1, Jeremy F Reiter1
1Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Cell
|July 15, 2017
概括
随着年龄的增长或肌肉衰竭而导致骨肌肉再生受损. 阻断纤维/脂肪原体 (FAPs) 上的初级毛可以防止脂肪的形成,并增强肌肉的修复.
科学领域:
- 肌肉再生和修复
- 细胞信号通道
- 脂肪生成和纤维化
背景情况:
- 随着年龄的增长和肌肉衰竭,骨肌肉的再生下降,导致脂肪透.
- 肌肉中的纤维/脂肪原生细胞 (FAP) 分化为脂肪细胞,导致脂肪退化.
- FAP上的初级毛对于感知和转换细胞间信号至关重要,比如 (Hh).
研究的目的:
- 在骨肌肉再生和脂肪退化的FAPs的主要毛的作用进行调查.
- 确定由FAP初级眼调节的信号通路.
- 探索针对FAP毛的治疗策略,以对抗肌肉脂肪的替代.
主要方法:
- 在FAP中进行初级毛的遗传切除.
- 在受伤后的肌肉再生和脂肪生成的分析和杜申肌肉衰竭小鼠模型.
- 研究Hh信号通路组件和下游目标,包括TIMP3和MMP14.
- 使用TIMP3模拟剂的药理抑制FAP脂肪生成.
主要成果:
- 在受伤和杜申肌肉衰竭模型中,从FAP中遗传去除乳毛抑制了肌内脂肪生成.
- 阻断FAP纤维增强肌纤维再生并减少肌纤维大小的下降.
- 通过FAP乳毛调节TIMP3表达,从而抑制MMP14并阻断脂肪生成.
- 一种药理学TIMP3模拟剂阻止了FAP转化为脂肪细胞.
结论:
- 由FAPs发送的状刺信号是骨肌肉再生反应的关键调节者.
- 针对FAP初级毛和相关的信号通路提供了一种潜在的策略来预防骨肌肉中的脂肪退化.
- 了解FAP生物学对于开发与年龄相关的肌肉衰退和肌肉衰竭的治疗方法至关重要.
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