在COPD中,暴露会通过SIRT6调节的AKT/PI3K信号通路触发维门丁酸化
Rajesh Sinha1, Pooja Singh1, Huaxiu Zeng1
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
慢性阻塞性肺病 (COPD) 涉及呼吸道纤维化. 这项研究表明,可以抑制SIRT6,促进维门丁酸化,并恶化COPD的病原性.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 慢性阻塞性肺病 (COPD) 影响全球超过3亿人,由呼吸道纤维化和小呼吸道狭窄驱动.
- 暴露会诱导氧化应激,细胞外基质沉积和肺气道炎症.
- 纤维细胞功能障碍,包括细胞生长减少和循环素依赖性激酶抑制剂增加,有助于COPD的进展.
研究的目的:
- 为了调查sirtuin-6 (SIRT6) 在诱导的COPD病原体中的作用.
- 阐明将暴露,SIRT6,AKT/PI3K信号传递和维门酸化联系起来的分子机制.
- 评估SIRT6诱导在缓解COPD相关细胞变化的治疗潜力.
主要方法:
- 使用诱导的COPD小鼠模型.
- 研究了对SIRT6表达和AKT/PI3K信号通路的影响.
- 检查了对暴露和SIRT6调节的反应中的维门酸化.
- 采用siRNA转染来抑制维门丁和UBCS039在纤维细胞中诱导SIRT6.
主要成果:
- 暴露抑制了SIRT6,导致AKT/PI3K通路激活和维丁酸化.
- 由于SIRT6抑制,在暴露于的细胞中观察到细胞外维门的增加.
- 通过siRNA抑制维门并没有影响SIRT6,酸化AKT或PI3K水平.
- 用UBCS039诱导SIRT6,在暴露于的纤维细胞中减少了化AKT/PI3K和细胞外维门 (P=0.0002).
结论:
- 在调节维门丁酸化方面,SIRT6起着至关重要的作用.
- 对SIRT6的抑制有助于通过AKT/PI3K-vimentin轴对COPD的致病作用.
- 向SIRT6可能通过减少气道纤维化来为COPD提供一种新的治疗策略.
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