YAP活动可以防止呼吸机引起的肺损伤
Huan Liu1,2, Xuepeng Yang3, Feng Qi1
1Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Frontiers in physiology
|October 20, 2025
概括
刺激YES相关蛋白 (YAP) 活性通过增强肺修复机制来缓解呼吸器诱导的肺损伤 (VILI) 和肺纤维化. 抑制YAP会使VILI和纤维化恶化,强调YAP.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 机械呼吸 (MV) 可以引发炎症反应,导致呼吸器诱导的肺损伤 (VILI),肺修复受损和肺纤维化.
- 对YES相关蛋白 (YAP) 在VILI病变和肺组织修复中的特定作用尚不清楚.
研究的目的:
- 研究调节YAP活动对VILI,肺修复和纤维化的影响.
- 为了确定YAP抑制或刺激是否会影响MV的小鼠模型中的肺损伤结果.
主要方法:
- 使用高潮量通风 (HVT) 建立了MV诱导的肺损伤的小鼠模型.
- 在HVT之前,小鼠接受了YAP抑制剂 (脊椎蛋白) 或YAP刺激剂 (XMU-MP-1) 的治疗.
- 使用组织学和分子分析评估肺损伤,纤维化,膜上皮细胞 (AEC) 再生和YAP活性.
主要成果:
- 高密度肺炎加剧了肺损伤和纤维化,降低了AEC标记蛋白,并增加了YAP表达.
- 通过进一步减少AEC再生,YAP抑制使肺损伤和纤维化恶化.
- YAP刺激减轻了β-catenin的减少,改善了AEC再生,并缓解了肺损伤和纤维化.
结论:
- 调节YAP活动显著影响VILI结果.
- 刺激YAP活动显示出对VILI的保护作用,促进肺部修复和抑制纤维化.
- 针对YAP代表了管理VILI及其后续的潜在治疗策略.
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