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线粒体DNA通过TLR9-NF-κB-NLRP3轴诱导细胞核的细胞核灭

Peng Lu^1,2, Huayong Zheng², Hao Meng²

¹Chinese PLA Medical School, Beijing, China.

Journal of translational medicine

|June 15, 2023

概括

线粒体DNA (mtDNA) 通过TLR9-NF-κB-NLRP3通路触发细胞核脉细胞灭和椎间盘退化 (IVDD). 抑制mtDNA释放或TLR9激活为IVDD提供了潜在的治疗点.

科学领域:

生物医学科学生物医学科学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

核脉细胞 (NPC) 死亡在椎间盘退化 (IVDD) 中至关重要.
线粒体DNA (mtDNA) 作为与损伤相关的分子模式,可能激活炎症途径.
通过TLR9-NF-κB-NLRP3轴在NPC热和IVDD中mtDNA的作用尚不清楚.

研究的目的:

阐明mtDNA释放的机制及其在NPC热和IVDD中的作用.
研究TLR9-NF-κB-NLRP3信号通路在这个过程中的参与.
探索针对mtDNA释放或TLR9激活的潜在治疗策略.

主要方法:

构建了人体NPCs的体外氧化应激模型.
利用人类NP标本将分子标记与IVDD严重程度相关联.
开发了一种老鼠刺穿诱导的IVDD模型,以验证体内发现的结果.

主要成果:

在人类样本中,TLR9,NF-κB和NLRP3炎症体的表达与IVDD严重程度相关.
由氧化应激诱导的线粒体损伤引发的mtDNA释放激活了TLR9-NF-κB-NLRP3轴,导致NPC热.
抑制线粒体透性过渡孔 (mPTP) 开放或TLR9激活减弱的NPC热和IVDD.

结论:

mtDNA是通过TLR9-NF-κB-NLRP3轴的NPC热和IVDD的关键调解者.
向mtDNA释放或TLR9为椎间盘退化提供了有前途的治疗途径.

关键词:

椎间盘退化椎间盘退化在 NF-κBB 中.在NLRP3炎症酶体中,NLRP3炎症细胞的核是脉细胞.热灭菌的发生.在TLR9中,我们的mtDNA mtDNA

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