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Small. 2018 Apr;14(15):e1704008. doi: 10.1002/smll.201704008. Epub 2018 Mar 8.

Exosomal miRNA Profiling to Identify Nanoparticle Phagocytic Mechanisms.

Author information

1
Department of Occupational and Environmental Health, School of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.
2
School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, China.
3
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, 157 Jingliu Road, Jinan, 250001, China.
4
Department of Occupational Disease, Henan Provincial Institute of Occupational Health, Middle Street of Kangfu, Zhengzhou, 450052, China.
5
School of Basic Medicine, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, China.

Abstract

Inhaling a dangerous amount of nanoparticles leads to pulmonary inflammatory and immune disorders, which integrates several kinds of cells. Exosomes are suggested to play a crucial role in intercellular communication via miRNA transmission. To investigate the role of exosomal miRNA in nanoparticle phagocytosis, a total of 54 pneumoconiosis patients along with 100 healthy controls are recruited, exosomes derived from their venous blood are collected, and then exosomal miRNAs are profiled with high-throughput sequencing technology. miRNAs which are differentially expressed are used to predict target genes and conduct functional annotation. Interactions between miRNA hsa-let-7a-5p, hsa-let-7i-5p, and their cotarget gene WASL are found that can affect nanoparticle phagocytosis. The follow-up analysis of gene structure, tissue specificity, and miRNA-target gene regulatory mode supports the findings. Specially, the assumption is further confirmed via a series of cellular experiments, and the fibroblast transdifferentiate rate that is used as an indicator of nanoparticle phagocytosis decreased when elevating miRNA expression level. Thus, data in this study indicate that downregulation of miRNA hsa-let-7a-5p and hsa-let-7i-5p contributes to WASL elevation, promoting WASL and VASP complex formation, which is necessary for initiating Arp2/3 induced phagocytosis.

KEYWORDS:

exosomal miRNAs; intercellular communications; nanoparticles; phagocytosis; pneumoconiosis

PMID:
29516679
DOI:
10.1002/smll.201704008

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