卡尔潘促进LPS诱导的肺内皮屏障功能障碍通过塔林的裂变
Linjie Song1, Xiaofan Shi1, Laszlo Kovacs1,2
1Department of Pharmacology & Toxicology.
American journal of respiratory cell and molecular biology
|August 28, 2023
概括
卡尔帕因激活切割了塔林,破坏了急性肺损伤 (ALI) 中的肺内皮屏障. 抑制calpain或talin裂变可以防止LPS诱导的肺屏障功能障碍和水.
科学领域:
- 细胞生物学 细胞生物学
- 病理生理学 病理生理学
- 分子医学是分子医学.
背景情况:
- 急性肺损伤 (ALI) 涉及肺血管内皮细胞 (EC) 屏障损害,导致透性增加和肺.
- 像脂聚糖化物 (LPS) 这样的格拉姆阴性细菌毒素是主要的ALI原因,激活托尔样受体4 (TLR4) 并破坏EC屏障.
- 在ALI中中介于LPS诱导的细胞骨重组和EC屏障破坏的信号通路尚未完全理解.
研究的目的:
- 调查calpain和talin在LPS诱导的ALI中肺微血管EC屏障破坏中的作用.
- 阐明将LPS,calpain,talin和EC屏障完整性联系在一起的分子机制.
主要方法:
- 使用了人类肺部微血管EC和*in vivo*ALI模型的*体外*研究.
- 研究了LPS对calpain激活,talin裂变,RhoA激活和髓轻链 (MLC) 酸化的影响.
- 采用了calpain抑制,talin knockdown和talin域/突变物的过度表达,以评估它们对EC屏障功能的影响.
主要成果:
- LPS诱导calpain激活和talin裂变,导致RhoA激活和EC屏障破坏.
- 卡尔帕因抑制减轻了塔林裂变,RhoA激活和LPS诱导的肺EC屏障功能障碍和.
- 塔林倒置或使用抗裂变的塔林突变物减轻了LPS诱导的EC屏障破坏.
结论:
- 在ALI中,calpain介导的塔林裂变是LPS诱导的肺微血管EC屏障破坏的关键途径.
- 针对calpain-talin相互作用可能为ALI提供治疗策略.
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