Lung contusion drives lung injury by modifying miRNA cargo in alveolar small extracellular vesicles.

IF 4.8 3区 医学 Q2 CELL BIOLOGY
Keita Nakatsutsumi, Dong Jun Park, Wooil Choi, William Johnston, Katie Pool, Jenny Kezios, Raul Coimbra, Brian P Eliceiri, Todd W Costantini
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引用次数: 0

Abstract

Objective: To evaluate the micro-RNA (miRNA) cargo of alveolar small extracellular vesicles (sEVs) after lung contusion (LC), which can contribute to the development of trauma-related acute lung injury (ALI).

Methods: A mouse model of LC was conducted with a controlled cortical impact device. Bronchoalveolar lavage fluid (BAL) was collected 24 h post-injury and sEVs were purified using size exclusion chromatography. sEVs characteristics and miRNA cargo were analyzed with vesicle flow cytometry and sequencing. Macrophages were treated with BAL sEVs in vitro to assess their pro-inflammatory effect.

Results: LC increased lung permeability and caused ALI histologically. LC increased the number of sEVs in the BAL and altered their miRNA cargo. BAL sEVs collected after LC increased pro-inflammatory cytokine release from macrophages.

Conclusion: LC increased the mobilization of sEVs to the alveolar space and modified their miRNA cargo that might contribute to the development of ALI by activating the immune response in macrophages.

肺挫伤通过改变肺泡小细胞外囊泡中的miRNA货物驱动肺损伤。
目的:探讨肺挫伤(LC)后肺泡小细胞外囊泡(sev)的微rna (miRNA)载量在创伤性急性肺损伤(ALI)发生中的作用。方法:采用可控皮质冲击装置建立小鼠LC模型。损伤后24 h收集支气管肺泡灌洗液(BAL),用大小排斥色谱法纯化sev。利用囊泡流式细胞术和测序技术分析sev特征和miRNA货量。用BAL sev体外处理巨噬细胞以评估其促炎作用。结果:LC增加肺通透性,在组织学上引起ALI。LC增加了BAL中sev的数量并改变了它们的miRNA载货量。LC后收集的BAL sev增加巨噬细胞的促炎细胞因子释放。结论:LC增加了sev向肺泡空间的动员,并改变了它们的miRNA载货,这可能通过激活巨噬细胞的免疫反应来促进ALI的发展。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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