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YTHDF2依赖的m6FOXO3mRNA的修改调解TIMP1的表达,并导致ROS刺激后的椎间盘退化

Fei Wang¹, Yifeng Wang², Songou Zhang¹

¹Department of Orthopedic Surgery, Shaoxing Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.

Cellular and molecular life sciences : CMLS

|December 3, 2024

概括

反应性氧物种 (ROS) 通过通过YTHDF2.2.降解FOXO3 mRNA驱动椎间盘退化 (IDD). 抑制YTHDF2恢复FOXO3和TIMP1,减少矩阵降解并减轻IDD.

科学领域:

生物化学生物化学
分子生物学分子生物学
再生医学是一种再生医学.

背景情况:

反应性氧物种 (ROS) 积累是椎间盘退化 (IDD) 的关键因素.
连接ROS与IDD病原体的精确分子机制尚未完全理解.

研究的目的:

阐明ROS对IDD有所贡献的分子机制.
确定IDD的潜在治疗点.

主要方法:

从年轻和老年小鼠的椎间盘 (IVD) 的比较分析.
使用过氧化 (H2O2) 诱导腰椎间盘中的ROS.
对于相对和绝对定量 (iTRAQ) 蛋白质组学分析的异标签.
对YTHDF2/FOXO3/TIMP1/MMPs信号轴的研究.
在体内对YTHDF2抑制剂 (DC-Y13-27) 的评估.

主要成果:

老年和H2O2治疗的小鼠在IVD中呈现高ROS,YTHDF2和MMP的增加,以及FOXO3和TIMP1水平的降低.
ROS激活了YTHDF2,导致m6A修饰的FOXO3mRNA降解,减少TIMP1表达,并增加了MMP活性.
通过DC-Y13-27抑制YTHDF2,恢复FOXO3和TIMP1水平,抑制MMP活性,并在老年和H2O2治疗的小鼠中改善IDD.

结论:

一个涉及YTHDF2,FOXO3,TIMP1和MMP的新ROS调节通路驱动IDD.
向YTHDF2为缓解椎间盘退化提供了一个有希望的治疗策略.

关键词:

在FOXO3中使用FOXO3.椎间盘退化椎间盘退化在MMP中,MMP是MMP.有反应性氧物种的反应性氧物种.时间表1 时间表1 这就是YTHDF2的原因.

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