未折叠的蛋白质反应抑制增强了牛肺动脉内皮细胞中LPS诱导的屏障功能障碍和炎症
Nektarios Barabutis1, Mohammad S Akhter1
1School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisiana, USA.
Tissue barriers
|July 12, 2023
概括
4-Phenylbutyrate (4-PBA),一个未折叠的蛋白质反应 (UPR) 抑制剂,加剧了LPS诱导的内皮损伤和肺细胞中的屏障破坏. 这表明,抑制UPR可能会增加与败血症相关的损伤.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病理生理学 病理生理学
背景情况:
- 败血症和急性呼吸困难综合征由于屏障功能障碍而带来显著的死亡风险.
- 针对屏障完整性的新型治疗策略至关重要.
研究的目的:
- 为了研究4-Phenylbutyrate (4-PBA) 的影响,一个未折叠的蛋白质反应 (UPR) 抑制剂,Lipopolysaccharides (LPS) 诱导的内皮损伤.
- 为了确定4-PBA是否会加剧或减轻LPS诱导的肺内皮细胞损伤.
主要方法:
- 使用的牛肺内皮细胞暴露于脂聚糖 (LPS).
- 给定了4-Phenylbutyrate (4-PBA),并评估了它对UPR标记物,STAT3和ERK信号通路以及内皮细胞透性的影响.
- 在中度度下评估细胞活力.
主要成果:
- 4-PBA抑制了BiP,这是UPR激活的标志物.
- 4-PBA强化LPS诱导的STAT3和ERK1/2信号通路的激活.
- 4-PBA在炎症的内皮细胞中增强了对细胞的超透性,而不会影响中等剂量的细胞活力.
结论:
- 使用4-PBA抑制UPR会增加LPS诱导的内皮损伤.
- 4-PBA在炎症的肺内皮细胞中加剧屏障破坏.
- 这些发现表明,UPR抑制在诸如败血症等疾病中的潜在有害作用.
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