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.
Bibliographical noteFunding 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).
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- nuclear factor κB
- preterm birth
- tumor necrosis factor receptor associated factor 6
ASJC Scopus subject areas
- Reproductive Medicine
- Molecular Biology
- Obstetrics and Gynaecology
- Developmental Biology
- Cell Biology