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TRIM59在肺高血压中的作用:调节蛋白质无处不在修饰的调节
Yingli Liu1, Li Zhu1,2, Yue Ming1
1Department of Pulmonary and Critical Care Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, People's Republic of China.
Journal of translational medicine
|November 18, 2023
概括
三方基因含蛋白59 (TRIM59) 在肺高血压 (PH) 中表达高,促进肺动脉光滑肌细胞增殖和血管重塑. TRIM59是治疗PH的潜在治疗标.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 肺部医学 肺部医学
背景情况:
- 肺高血压 (PH) 涉及过度的肺血管改造和光滑肌肉细胞增殖.
- 驱动PH病变的分子机制在很大程度上是未知的.
- 识别这些机制对于开发有效的PH治疗至关重要.
研究的目的:
- 研究不同表达基因在PH中的作用.
- 为了确定PH治疗的新型分子标.
- 阐明TRIM59在PH中的功能和调节.
主要方法:
- 对PH患者的基因表达数据的分析 (GSE113439).
- 在患者组织,动物模型和细胞培养中验证TRIM59表达.
- 功能增益和丧失研究,以评估TRIM59对细胞增殖和PH病理的影响.
- 使用蛋白质组学和质谱学研究YAP1/TEAD4的转录调节和TRIM59的蛋白质点.
主要成果:
- 在PH患者和PH大鼠模型的肺动脉中,TRIM59的调节显著上升.
- TRIM59的过度表达增强了肺动脉平滑肌肉细胞的增殖,而沉默则抑制了它.
- 在PH大鼠中,TRIM59静音减轻心脏和肺损伤,减轻肺血管重塑.
- YAP1/TEAD4积极调节TRIM59转录,TRIM59直接向34种蛋白质,影响蛋白质无处不在.
结论:
- TRIM59通过促进PASMC增殖和血管重塑,是PH病变发生的关键驱动因素.
- TRIM59代表了肺高血压的有前途的治疗标.
- 了解TRIM59的调节途径和蛋白质相互作用可能会提供新的治疗策略.
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