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间歇性循环机械压缩通过扰乱Nrf2/PINK1信号通路依赖的线粒细胞衰变来促进末端状细胞的退化
Quan Zheng1, Chuan-Dong Wang2, Song Shao1
1Department of Orthopedic Surgery, Luan Hospital Affiliated to Anhui Medical University, Luan, 237001, Anhui, China.
Human cell
|August 3, 2023
概括
间歇性循环机械压缩 (ICMC) 通过抑制Nrf2/PINK1通路,从而导致退化,从而损害端板冠状细胞的线粒细胞衰变. 准这种途径可能为预防磁盘退化提供治疗策略.
科学领域:
- 生物医学工程 生物医学工程
- 细胞生物学 细胞生物学
- 整形外科 整形外科 整形外科
背景情况:
- 异常的机械负荷驱动端板软骨退化,这是椎间盘退化的前体.
- 已知间歇性循环机械压缩 (ICMC) 促进端板状细胞退化,但潜在的机制尚不清楚.
研究的目的:
- 为了研究PTEN诱导的激酶1 (PINK1) 依赖于线粒细胞的作用,在ICMC诱导的端板冠状细胞退化.
- 在ICMC下,确定NF-E2相关因子2 (Nrf2) 激活,PINK1依赖的线粒细胞衰变和末板红细胞中氧化应激抵抗之间的相关性.
主要方法:
- 建立了机械压缩诱导的端板状细胞退化体外和体内模型.
- 在ICMC下评估了细胞外基质降解,PINK1介导的线粒体衰变,线粒体反应性氧物种 (ROS) 生成和Nrf2通路激活 (表达,Keap1相互作用,核转位).
- 利用Nrf2过度表达和PINK1小RNA来评估它们对状细胞退化和线粒细胞衰变的影响.
主要成果:
- ICMC促进了端板冠状细胞细胞外细胞矩阵的降解.
- 在ICMC下,PINK1介导的线粒被抑制,而线粒体ROS生成增加.
- ICMC抑制了Nrf2表达,Keap1相互作用和核转位.
- Nrf2的过度表达降低了ROS,并逆转了ICMC诱导的慢性细胞退化,这种效应部分依赖PINK1介导的线粒细胞衰变.
结论:
- ICMC 抑制了 Nrf2/PINK1 信号通路,降低了线粒和增加了氧化应激,从而促进了端板冠状细胞退化.
- 治疗对Nrf2/PINK1信号通路的调节为缓解末端状细胞退化和椎间盘退化提供了潜在的合成药物策略.
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