抑制CILP2通过Wnt信号通路改善糖代谢和 Sarcopenia中的线粒体功能障碍
Zhibo Deng1,2, Chao Song1,2, Long Chen1,2
1Shengli Clinical Medical College, Fujian Medical University, Fuzhou, People's Republic of China.
Journal of cachexia, sarcopenia and muscle
|October 10, 2024
概括
软骨酸性蛋白1 (CILP2) 在衰老的肌肉和肉症中升高,损害葡萄糖代谢和胰岛素敏感性. 准CILP2可能为与年龄相关的肌肉损失提供治疗效益.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 老年学是一门学科.
背景情况:
- 骨肌对于葡萄糖代谢和胰岛素敏感性至关重要.
- 软骨酸性蛋白1 (CILP2) 水平升高表明葡萄糖耐受性受损,在骨肌肉中发现.
- 在与年龄相关的肌肉缩,葡萄糖平衡和胰岛素敏感性中CILP2的作用尚未完全理解.
研究的目的:
- 研究CILP2在与年龄相关的骨肌肉缩中的作用.
- 为了确定CILP2对葡萄糖平衡和肌肉胰岛素敏感性的影响.
- 阐明CILP2在肌肉中的功能背后的分子机制.
主要方法:
- 在老年小鼠和肉患者中评估CILP2表达.
- 在C2C12神经细胞中利用了用于CILP2操纵 (沉默/过度表达) 的lentiviral载体.
- 采用了各种测定方法,包括免疫光学,西部涂抹,qPCR,RNA测序,葡萄糖吸收,双化酶记者测定和CO-IP.
- 在SAMP8小鼠中使用腺相关病毒-9实体研究CILP2淘汰疗效.
主要成果:
- 在老年小鼠和肉患者中,CILP2的表达显著更高.
- 过度表达CILP2减少了肌肉细胞的增殖,分化,葡萄糖吸收和胰岛素敏感性,同时增加了缩标志物.
- 在老年小鼠中,通过Wnt/β-catenin通路介导的CILP2敲击改善了肌肉功能,质量和葡萄糖代谢.
- RNA测序确定了Wnt信号传递作为关键途径,Wnt3a被证实是相互作用的蛋白质.
结论:
- CILP2与Wnt3a相互作用,抑制了Wnt/β-catenin通路.
- 这种抑制导致胰岛素敏感性受损和骨肌肉中的葡萄糖代谢.
- 准CILP2是一个潜在的治疗策略.
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