DDIT3驱动细胞核脉细胞 PANoptosis 和椎间盘退化进展
Kun Wang1, Hangyu Ji2, Jiawei Gao3
1Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Apoptosis : an international journal on programmed cell death
|January 10, 2026
概括
可诱导DNA损伤的转录3 (DDIT3) 在细胞核中驱动炎症性PANoptosis,导致椎间盘退化. 准DDIT3-CUL3-caspase-8通路可能为IDD提供新的治疗方法.
科学领域:
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
- 生物化学 生物化学
背景情况:
- 椎间盘退化 (IDD) 与通过PANoptosis (亡,亡,烧亡) 的细胞死亡有关.
- 这种细胞死亡的分子调节者仍然在很大程度上是未知的.
研究的目的:
- 确定NP细胞中炎症性PANoptosis的关键调节者.
- 研究DDIT3在IDD病原体中的作用.
- 阐明将DDIT3与PANoptosis和IDD联系起来的分子机制.
主要方法:
- 用TNF-α治疗的人类NP细胞的RNA测序.
- 在体外 Knockdown/过度表达DDIT3.
- 染色体免疫沉 (ChIP) 和电泳性移动性转移试验 (EMSA).
- 分子对接和共同免疫沉.
- 在老鼠IDD模型中的体内lentiviralDDIT3沉默.
主要成果:
- 在退化的磁盘中,DDIT3被上调,并促进炎症性PANoptosis标记物,炎症性细胞因子和ROS.
- DDIT3对CUL3进行交换激活,CUL3与酶-8激活相互作用并促进激活.
- 在体内对DDIT3进行静音减轻IDD,保存细胞外基质,并减少PANoptosis.
- 在IDD模型中,DDIT3过度表达加速了矩阵损失.
结论:
- DDIT3-CUL3-caspase-8轴是NP细胞中炎症性PANoptosis的一个关键调节器.
- DDIT3是阻止椎间盘退化进展的潜在治疗标.
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