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急性呼吸困扰与健康的肺环境不同地影响介质细胞流体细胞细胞外囊 miRNAs

Sara Rolandsson Enes¹, Irakli Dzneladze², Thomas H Hampton³

¹Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA; Department of Experimental Medical Science, Faculty of Medicine, Lund University, Lund, Sweden.

|February 13, 2025

概括

介酶体 stromal 细胞 (MSC) 衍生的细胞外囊泡 (EVs) 携带微RNA (miRNAs),在急性呼吸困扰综合征 (ARDS) 中发生变化. 这些ARDS改变的EV-miRNAs影响肺上皮细胞功能,可能会影响粘膜细胞清除.

科学领域:

细胞生物学细胞生物学
基因组学就是基因组学.
肺部医学肺部医学

背景情况:

急性呼吸困扰综合征 (ARDS) 涉及炎症,改变了介质细胞 stromal 细胞 (MSC) 的表达.
尚不清楚ARDS对MSC衍生的细胞外囊泡 (EVs) 中微RNA (miRNA) 含量的影响.

研究的目的:

调查暴露于ARDS患者支气管支气管洗液 (BALF) 后MSC-EVs的miRNA配置文件的变化.
探索这些miRNA改变对肺上皮细胞的功能后果.

主要方法:

来自人类骨髓衍生的MSCs (hMSCs) 的miRNAs的测序分析暴露在ARDS患者和健康志愿者 (HV) 的ex vivoBALF中.
生物信息分析包括分辨,差异表达和网络分析,以确定关键的miRNA和途径.
功能性试验评估hMSC-EVs对囊性纤维化转膜导电调节器 (CFTR) 介导的支气管上皮细胞中化物分泌的作用.

主要成果:

与HV BALF相比,在暴露于ARDS BALF后的hMSC-EV中,有14个miRNA被显著改变.
一个监管网络确定了四个关键的miRNAs (miR-760,miR-3175,miR-885-3p,miR-766-3p),可能共同准特定的基因路径.
参与CFTR调节的两个特定的miRNAs (miRNA-145-5p,miRNA-138-5p) 在ARDS BALF暴露的hMSC-EV中增加.
来自ARDS BALF暴露的hMSCs的EVs对CFTR介导的化物分泌有差异性的影响,预测粘膜细胞清除率降低.

结论:

在BALF中ARDS相关的变化改变了hMSC-EVs的miRNA载荷.
这些改变的hMSC-EV小RNA可能在调节肺上皮细胞功能,特别是CFTR活性方面发挥作用.
需要进一步的研究,以了解hMSC-EVmiRNAs在ARDS病原和粘膜功能障碍中的临床影响.

关键词:

在CFTR中,CFTR是最重要的.急性呼吸困扰综合征是什么支气管支气管洗液的支气管支气管外基因组是外基因组的组成部分.细胞外囊泡中的细胞外囊泡.介质细胞层层细胞.这是一个小RNARNA.

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相关概念视频

Mesenchymal Stem Cells

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...