From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

Frazier, S., McBride, M. W. , Mulvana, H. and Graham, D. (2020) From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia. Clinical Science, 134(8), pp. 1001-1025. (doi: 10.1042/CS20200023) (PMID:32337535) (PMCID:PMC7239341)

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Abstract

Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

Item Type:Articles
Keywords:microRNA, placenta, preeclampsia, pregnancy.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Frazier, Sonya and McBride, Dr Martin and Graham, Dr Delyth
Authors: Frazier, S., McBride, M. W., Mulvana, H., and Graham, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:27 April 2020
Copyright Holders:Copyright© 2020 The Author(s)
First Published:First published in Clinical Science 134(8):1001-1025
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences