PMID- 31588496
OWN - NLM
STAT- MEDLINE
DCOM- 20200623
LR  - 20200623
IS  - 1460-2407 (Electronic)
IS  - 1360-9947 (Linking)
VI  - 25
IP  - 11
DP  - 2019 Nov 30
TI  - Anti-inflammatory effects of mesenchymal stem cell-derived exosomal 
      microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells.
PG  - 755-771
LID - 10.1093/molehr/gaz054 [doi]
AB  - 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 kappaB, 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.
CI  - (c) 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: journals.permissions@oup.com.
FAU - Yang, Changwon
AU  - Yang C
AD  - Institute of Animal Molecular Biotechnology and Department of Biotechnology, 
      College of Life Sciences and Biotechnology, Korea University, Seoul 02841, 
      Republic of Korea.
FAU - Lim, Whasun
AU  - Lim W
AD  - Department of Food and Nutrition, Kookmin University, Seoul 02707, Republic of 
      Korea.
FAU - Park, Junghyun
AU  - Park J
AD  - Institute of Animal Molecular Biotechnology and Department of Biotechnology, 
      College of Life Sciences and Biotechnology, Korea University, Seoul 02841, 
      Republic of Korea.
FAU - Park, Sunwoo
AU  - Park S
AD  - Institute of Animal Molecular Biotechnology and Department of Biotechnology, 
      College of Life Sciences and Biotechnology, Korea University, Seoul 02841, 
      Republic of Korea.
FAU - You, Seungkwon
AU  - You S
AD  - Institute of Animal Molecular Biotechnology and Department of Biotechnology, 
      College of Life Sciences and Biotechnology, Korea University, Seoul 02841, 
      Republic of Korea.
FAU - Song, Gwonhwa
AU  - Song G
AD  - Institute of Animal Molecular Biotechnology and Department of Biotechnology, 
      College of Life Sciences and Biotechnology, Korea University, Seoul 02841, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Hum Reprod
JT  - Molecular human reproduction
JID - 9513710
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MIRN146 microRNA, human)
RN  - 0 (MIRN548 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Amniotic Fluid/cytology
MH  - Animals
MH  - Cell Line
MH  - Cell Movement/genetics
MH  - Exosomes/genetics
MH  - Humans
MH  - Inflammation/pathology
MH  - Inflammation Mediators/*metabolism
MH  - Lipopolysaccharides
MH  - MAP Kinase Signaling System/physiology
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - MicroRNAs/*genetics
MH  - NF-kappa B/metabolism
MH  - Trophoblasts/*physiology
OTO - NOTNLM
OT  - exosome
OT  - inflammation
OT  - lipopolysaccharide
OT  - migration
OT  - nuclear factor kappaB
OT  - preterm birth
OT  - trophoblast
OT  - tumor necrosis factor receptor associated factor 6
EDAT- 2019/10/08 06:00
MHDA- 2020/06/24 06:00
CRDT- 2019/10/08 06:00
PHST- 2019/02/18 00:00 [received]
PHST- 2019/09/03 00:00 [revised]
PHST- 2019/09/09 00:00 [accepted]
PHST- 2019/10/08 06:00 [pubmed]
PHST- 2020/06/24 06:00 [medline]
PHST- 2019/10/08 06:00 [entrez]
AID - 5581899 [pii]
AID - 10.1093/molehr/gaz054 [doi]
PST - ppublish
SO  - Mol Hum Reprod. 2019 Nov 30;25(11):755-771. doi: 10.1093/molehr/gaz054.