Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells

Changwon Yang, Whasun Lim, Junghyun Park, Sunwoo Park, Seungkwon You, Gwonhwa Song

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    57 Citations (Scopus)

    Abstract

    Human umbilical cord mesenchymal stem cells (MSCs) have been reported to improve the migration and invasion of trophoblast cells; however, little is known about whether MSC-derived exosomes and exosomal miRNAs can regulate trophoblast cell properties. In this study, we investigated whether exosomal miRNAs from amniotic fluid-derived MSC (AF-MSC) could regulate the inflammatory response of the human trophoblast cell line HTR8/SVneo. We verified the anti-inflammatory effects of AF-MSCs on lipopolysaccharide (LPS)-induced inflammatory trophoblast cells and found that miR-146a-5p and miR-548e-5p in the AF-MSC-derived exosomes regulate nuclear factor κB, AKT and mitogen-activated protein kinase protein phosphorylation. Furthermore, we found that the transfection of human trophoblast cells with miR-146a-5p and miR-548e-5p inhibitors reduced trophoblast migration (P < 0.05 vs control) and the expression of proliferating cell nuclear antigen, a protein essential for cell proliferation (P < 0.01 vs control). In particular, the miR-548e-5p inhibitor induced apoptosis, while tumor necrosis factor receptor-associated factor 6, a predicted target of miR-146a-5p and miR-548e-5p, was involved in the regulation of oxidative stress in the human trophoblast cells. In a mouse model of LPS-induced preterm birth (PB), miR-146a-5p expression was found to be relatively low in the group in which the effect of AF-MSCs was insignificant. However, this study is limited in that the changes in the expression of some genes in response to AF-MSCs differ between the cell line and mouse model. Collectively, these data show that exosomal miR-146a-5p and miR-548e-5p from AF-MSCs have anti-inflammatory effects on human trophoblast cells and may be novel targets for treating inflammatory diseases and associated problems that occur during pregnancy, such as PB.

    Original languageEnglish
    Pages (from-to)755-771
    Number of pages17
    JournalMolecular human reproduction
    Volume25
    Issue number11
    DOIs
    Publication statusPublished - 2019 Nov 1

    Bibliographical note

    Funding Information:
    This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health &Welfare (grant no. HI17C0929) and the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (no. 2018R1C1B6009048).

    Publisher Copyright:
    © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: [email protected].

    Keywords

    • exosome
    • inflammation
    • lipopolysaccharide
    • migration
    • nuclear factor κB
    • preterm birth
    • trophoblast
    • tumor necrosis factor receptor associated factor 6

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Embryology
    • Molecular Biology
    • Genetics
    • Obstetrics and Gynaecology
    • Developmental Biology
    • Cell Biology

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