是的相关蛋白诱导肺内皮的年龄相关的炎症信号
Memet T Emin1, Alexandra M Dubuisson1,2, Prisha Sujin Kumar1
1Pediatric Critical Care, Hospitalist, and Palliative Medicine, Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, United States.
概括
在成年小鼠肺内皮中,YAP信号驱动急性肺损伤 (ALI) 中的炎症,与青少年不同. 阻止YAP可以保护成年小鼠,这表明儿科急性呼吸困扰综合征 (ARDS) 治疗的年龄依赖途径.
科学领域:
- 肺部医学 肺部医学
- 细胞信号传输 细胞信号传输
- 炎症研究 炎症研究
背景情况:
- 急性肺损伤 (ALI) 导致急性呼吸困难综合征 (ARDS),这种疾病治疗选择有限,成人死亡率高于儿童.
- 成人和幼年动物之间的生理差异可能解释了ALI/ARDS结果的差异,这是动物模型研究表明的.
研究的目的:
- 在肺炎诱导的ALI期间调查肺内皮内炎信号通路的年龄相关差异.
- 确定YES相关蛋白 (YAP) 信号在成年小鼠与幼年小鼠的ALI发病过程中的作用.
主要方法:
- 在成年和21天大的断奶小鼠中,肺炎诱导的ALI模型.
- 对内皮炎症信号的分析,包括YAP和核因子-kappa B (NF-κB) 激活.
- 肺内皮细胞的转录分析.
- 在成年小鼠中对YAP信号的药理学阻断.
主要成果:
- 肺炎诱导的ALI在成年小鼠肺内皮中触发了炎症信号,依赖于YAP,但这在断奶小鼠中不存在.
- 转录组分析显示,与断奶婴儿相比,成年ALI肺部的NF-κB激活显著增加.
- 在成年小鼠中阻断YAP信号,在*Pseudomonas aeruginosa*肺炎期间减轻了炎症,低氧化和NF-κB转位.
结论:
- 成年肺内皮中依赖于YAP的信号级联有助于ALI的发病,但在断奶小鼠中不存在.
- 这些年龄相关的信号差异可能部分解释了儿童ARDS与成人ARDS相比的更好的结果.
- 针对特定年龄段的途径为不同年龄段的ARDS提供了潜在的治疗策略.
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