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Pro-inflammatory cytokine-induced microRNA-212-3p expression promotes myocyte contraction via methyl-CpG-binding protein 2: a novel mechanism for infection-related preterm parturition.
- Source :
-
Molecular human reproduction [Mol Hum Reprod] 2019 May 01; Vol. 25 (5), pp. 274-282. - Publication Year :
- 2019
-
Abstract
- Preterm labour is a common pregnancy complication contributing to major maternal and fetal morbidity and mortality. We have found microRNA (miR)-212-3p, a potential infection-associated molecule, was significantly over-expressed during human preterm labour. However, the mechanism remains unknown. In this study, we have adopted a lipopolysaccharide (LPS)-induced Institute of Cancer Research murine preterm model to examine the role of miR-212-3p in the infection-induced preterm labour. Myometrial miR-212-3p expression was increased by nearly 4-fold in the term labour group (P = 0.10) and 12-fold (P = 0.03) in the LPS-induced preterm labour group compared with the non-labour group. In vitro cellular experiments confirmed that a series of pro-inflammatory cytokines, including interleukin (IL)1B (P = 0.02) and IL-6 (P = 0.01), rather than LPS (P = 0.08) itself could significantly upregulate miR-212-3p expression in human myometrial smooth muscle cells. Methyl-CpG-binding protein 2 (MeCP2), as a target gene of miR-212-3p confirmed by our dual luciferase assay, influenced myocyte contractility and connexin 43 expression which is an important contraction-associated protein. Therefore, we conclude that miR-212-3p may be involved in infection-induced preterm labour through MeCP2 and it is a promoting molecule and novel target for the diagnosis and treatment of preterm labour in the future.<br /> (© 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 email: journals.permissions@oup.com.)
- Subjects :
- Animals
Base Sequence
Connexin 43 genetics
Connexin 43 metabolism
Female
Gene Expression Regulation
Genes, Reporter
Humans
Infant, Newborn
Interleukin-1beta pharmacology
Interleukin-6 pharmacology
Luciferases genetics
Luciferases metabolism
Methyl-CpG-Binding Protein 2 metabolism
Mice
Mice, Inbred ICR
MicroRNAs agonists
MicroRNAs metabolism
Models, Animal
Myocytes, Smooth Muscle cytology
Myocytes, Smooth Muscle metabolism
Myometrium cytology
Myometrium drug effects
Myometrium metabolism
Obstetric Labor, Premature chemically induced
Obstetric Labor, Premature metabolism
Obstetric Labor, Premature pathology
Pregnancy
Lipopolysaccharides pharmacology
Methyl-CpG-Binding Protein 2 genetics
MicroRNAs genetics
Myocytes, Smooth Muscle drug effects
Obstetric Labor, Premature genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2407
- Volume :
- 25
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular human reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 30892651
- Full Text :
- https://doi.org/10.1093/molehr/gaz005