血小板衍生的细胞外囊泡通过输送ARF6恶化败血性急性损伤
Xun Lu1,2, Guiya Jiang1,2, Yue Gao1,2
1Department of Urology, Affiliated Zhongda hospital of Southeast University, Nanjing, China.
International journal of biological sciences
|November 6, 2023
概括
血小板衍生的细胞外囊泡 (EVs) 通过激活ARF6通路,恶化败血症诱导的急性损伤 (AKI). 抑制血小板EVs或ARF6显示了感染性AKI的治疗潜力.
科学领域:
- 生物医学研究的研究.
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 循环的细胞外囊泡 (EVs) 参与了与败血症相关的器官功能障碍.
- 血小板衍生的EVs在败血症引起的急性损伤 (AKI) 中的特定作用尚不清楚.
研究的目的:
- 为了研究血小板衍生的EVs在败血症诱导的AKI中的作用.
- 确定血小板EVs加剧AKI的分子机制.
- 探索治疗策略以向血小板EVs在败血症AKI.
主要方法:
- 从用脂多糖 (LPS) 或酸盐缓冲盐液 (PBS) 刺激的人类血小板中分离出了EV.
- 在实验室中,PBS-EVs和LPS-EVs被施用给接受结和穿孔 (CLP) 的小鼠或LPS刺激的管状上皮细胞 (RTECs).
- 定量蛋白质组学确定了差异性蛋白质,并分析了信号通路.
- 使用了关键分子的遗传和药理抑制.
主要成果:
- 通过增加亡,炎症和氧化应激,LPS-EVs加剧了败血症AKI.
- 在LPS-EV中,ADP-ribosylation factor 6 (ARF6) 被确定为一个关键蛋白质.
- ERK/Smad3/p53信号的ARF6激活加剧了AKI;RTEC中的LPS诱导的ARF6上调涉及TLR4/MyD88通路.
- 抑制ARF6或血小板分泌改善了败血症AKI.
结论:
- 血小板衍生的EVs有助于败血症诱导的AKI病原体.
- 在败血症期间,ARF6信号传递是EV诱导损伤的关键调解者.
- 向血小板激活和分泌是一个潜在的治疗途径呈现了败血性AKI.
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