子痫前期中微小RNA-206及其靶基因的差异表达
Differential expression of microRNA-206 and its target genes in preeclampsia.
作者信息
Akehurst Christine, Small Heather Y, Sharafetdinova Liliya, Forrest Rachel, Beattie Wendy, Brown Catriona E, Robinson Scott W, McClure John D, Work Lorraine M, Carty David M, McBride Martin W, Freeman Dilys J, Delles Christian
机构信息
aInstitute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK bKazan Federal University, Kazan, Russian Federation *Christine Akehurst and Heather Y. Small contributed equally to this work.
出版信息
J Hypertens. 2015 Oct;33(10):2068-74. doi: 10.1097/HJH.0000000000000656.
OBJECTIVES
Preeclampsia is a multisystem disease that significantly contributes to maternal and foetal morbidity and mortality. In this study, we used a nonbiased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with preeclampsia.
METHODS
Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed preeclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies.
RESULTS
From the microarray, we identified one miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and six miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation, only one miR-206 was found to be significantly increased in 28-week samples in women who later developed preeclampsia (1.4-fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with preeclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be downregulated (0.41 ± 0.04) in placental tissue from women with preeclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines.
CONCLUSION
Our pilot study has identified miRNA-206 as a novel factor upregulated in preeclampsia within the maternal circulation and in placental tissue.
目的
子痫前期是一种多系统疾病，对孕产妇和胎儿的发病率及死亡率有显著影响。在本研究中，我们采用无偏倚的微阵列方法来鉴定母体血浆中可能与子痫前期相关的新型循环微小RNA（miRNA）。
方法
在妊娠16周和28周时，从18名后来发展为子痫前期的女性（病例组）和18名血压正常妊娠的匹配女性（对照组）获取血浆样本。我们研究了血浆中的miRNA表达谱，随后在胎盘样本中确认了miRNA和靶基因的表达。胎盘样本取自一个独立队列，其中19名子痫前期女性与19名血压正常妊娠的女性相匹配。
结果
通过微阵列分析，我们鉴定出1种在妊娠16周时病例组和对照组之间有显著差异表达的miRNA，以及6种在妊娠28周时有显著差异表达的miRNA。经过定量聚合酶链反应（qPCR）验证，发现只有1种miR-206在后来发展为子痫前期的女性的28周样本中显著增加（变化倍数为1.4±0.2）。子痫前期女性的胎盘组织中也出现了miR-206表达增加的趋势。同时，miR-206的靶基因胰岛素样生长因子-1（IGF-1）在子痫前期女性的胎盘组织中也被发现下调（0.41±0.04）。在子宫肌层组织和滋养层细胞系中也可检测到miR-206的表达。
结论
我们的初步研究已鉴定出miRNA-206是子痫前期母体循环和胎盘组织中上调的一个新因素。
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