肺伤驱动肺损伤通过修改小胞外小细胞囊中的miRNA载荷
Keita Nakatsutsumi1,2, Dong Jun Park1, Wooil Choi1
1Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery, Department of Surgery, UC San Diego School of Medicine, 200 West Arbor Drive, San Diego, CA, 92103-8896, USA.
概括
肺部伤 (LC) 动员更多的小细胞外囊泡 (sEVs),携带肺部改变的微RNA (miRNAs). 这些sEV可以通过激活免疫细胞来驱动急性肺损伤 (ALI).
科学领域:
- 肺部医学 肺部医学
- 细胞外囊泡生物学 细胞外囊泡生物学
- 创伤研究 创伤研究
背景情况:
- 创伤引起的急性肺损伤 (ALI) 是一个重大的临床挑战.
- 小型细胞外囊泡 (sEVs) 参与细胞间通信.
- 膜 sEVs 在 ALI 发病过程中的作用尚不清楚.
研究的目的:
- 为了研究肺部伤 (LC) 后的膜sEVs的微RNA (miRNA) 含量.
- 确定改变的sEVmiRNA货物是否有助于与创伤相关的ALI.
主要方法:
- 通过使用可控皮质冲击装置,建立了LC的小鼠模型.
- 支气管支气管洗液 (BAL) 在受伤后24小时内收集.
- 通过尺寸排除色谱分离sEV,并使用囊泡流细胞计和测序进行表征.
- 在实验室中用BAL sEVs治疗巨细胞,以评估炎症反应.
主要成果:
- 肺部伤导致肺透率增加和ALI的组织学迹象.
- 在BAL液体中的sEV数量在LC后增加,其miRNA载荷发生了显著变化.
- 从LC小鼠中分离出来的sEVs诱导了巨细胞从巨细胞中释放的前炎性细胞因子.
结论:
- 肺部伤促进了sEVs释放到膜空间.
- 这些sEVs的改变的miRNA载荷可能在ALI发展中发挥作用.
- sEVs通过调节巨细胞免疫反应来促进ALI的发病.
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