细胞内膜网膜应激会通过激活TXNDC5来加剧缺血-再输液诱导的肺内皮屏障功能障碍
Yu Wang1, Pu Chen1, Shiqian Huang1
1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
Journal of advanced research
|December 28, 2025
概括
硫素域含有蛋白5 (TXNDC5) 的上调会通过破坏内皮屏障功能,加剧肺缺血-再输液损伤 (LIRI). 针对ER压力-TXNDC5通路为LIRI提供了一个潜在的治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
背景情况:
- 肺缺血-反损伤 (LIRI) 是一种严重的并发症,其特征是肺内皮屏障 (PEB) 功能障碍.
- 硫素域含有蛋白5 (TXNDC5) 在LIRI病原发生中的作用以前是未知的,尽管它已知在内皮稳定中的功能.
研究的目的:
- 调查TXNDC5在LIRI诱导的PEB中断中的作用.
- 在LIRI中探索TXNDC5的潜在机制.
- 评估LIRI中准TXNDC5通路的治疗潜力.
主要方法:
- 在老鼠和人类静脉内皮细胞中建立了LIRI模型.
- 使用AAV-shRNA调节的TXNDC5表达和药理上抑制的内分泌网膜 (ER) 应激.
- 检查了PEB结构/功能变化,包括HSP90/eNOS复合体稳定性.
- 使用ChIP-seq和救援实验调查了ATF6-TXNDC5轴.
- 通过血蛋白质组学验证了LIRI患者的发现,并构建了一个基于TXNDC5的诺姆图模型.
主要成果:
- 单细胞RNA测序揭示了LIRI中的TXNDC5上调,与PEB破坏,亡,ER压力和NF-κB激活相关.
- TXNDC5倒置恢复了内皮完整性和HSP90/eNOS的稳定性.
- ER压力通过ATF6促进了TXNDC5转录,并且药理上抑制ER压力减弱了LIRI.
- 患者血TXNDC5水平升高预测了LIRI及其严重程度,改善了早期预警模型.
结论:
- 由于ER压力引起的TXNDC5上调,通过损害HSP90/eNOS依赖的内皮功能,加剧LIRI.
- ER应力-TXNDC5信号通路是LIRI处理的一个独特的机制目标.
- TXNDC5作为早期LIRI检测和风险分层的潜在生物标志物.
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