在炎症过程中,Mmp12在巨细胞中被翻译调节
Silvia Kuntschar1, Giulia Cardamone1, Kevin Klann2
1Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, 60590 Frankfurt, Germany.
International journal of molecular sciences
|December 9, 2023
概括
巨细胞使用翻译控制来控制炎症. 通过调节矩阵金属化酶12 (MMP12) 生产和巨细胞迁移,化细胞或清除死细胞有助于解决炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 转录后调节对于适应性炎症反应至关重要.
- 在炎症解消过程中发生的转化性改变尚不清楚.
- 巨细胞 (Mφ) 在炎症及其解决过程中发挥关键作用.
研究的目的:
- 为了研究炎症解消阶段巨细胞的转化变化.
- 为了识别特定的翻译调节的蛋白质,参与了以细胞酶驱动的分辨率.
- 阐明矩阵金属酶12 (MMP12) 在炎症期间巨细胞迁移中的作用.
主要方法:
- 用LPS/IFNγ刺激的骨髓衍生巨细胞的转化变化的分析,并经历了细胞分裂.
- 总RNA测序以确认亲解析的转录签名.
- 量化 de novo 蛋白质合成以确定翻译性改变.
- 功能性试验评估MMP12对巨细胞迁移的影响.
主要成果:
- 细胞亡性细胞化 (efferocytosis) 在巨细胞中诱导了一种亲分辨签名.
- 尽管转录发生了轻微的变化,但在细胞和非细胞巨细胞之间观察到新的蛋白质合成的显著差异.
- 矩阵金属化酶12 (MMP12) 在早期炎症期间被翻译抑制,其翻译在解析过程中恢复.
- 减少MMP12的产生增强了巨细胞的矩阵依赖迁移.
结论:
- 翻译控制,而不仅仅是转录控制,在炎症期间显著影响巨细胞功能.
- 转化调节MMP12是控制巨细胞迁移的关键机制.
- 这种调节策略允许巨细胞在早期炎症期间迁移,并在解决过程中限制它,帮助有效的炎症反应和解决.
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