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miRNA在正常妊娠和子痫前期中发挥的调控网络:一项比较研究

The Regulatory Network Played by miRNAs During Normal Pregnancy and Preeclampsia: A Comparative Study.

作者信息

Ojeda-Casares Héctor, Paradisi Irene

机构信息

Laboratory of Human Genetics, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela.

出版信息

Microrna. 2021;10(4):263-275. doi: 10.2174/2211536611666211228100811.

Abstract

BACKGROUND

Preeclampsia is a pregnancy-specific syndrome, characterized by hypertension, proteinuria, and edema. Affecting between 2% and 8% of gestations worldwide, it accounts for 10% to 15% of maternal deaths. Although its etiology remains unclear, it includes complex pathological processes involving microRNAs, small non-coding RNA molecules with post-transcriptional repression effects on target mRNAs.

OBJECTIVE

To assess the expression of miRNAs during normal pregnancies and those complicated by preeclampsia, a sample of Venezuelan women were studied.

METHOD

Nine placental microRNAs (hsa-miR- 20a-5p, 21-3p, 26a-5p, 181a-5p, 199a-5p, 210-3p, 222-5p, 223-3p, 424-3p) were measured in maternal plasma during the second and third trimesters of normal pregnancies, using a SYBR Green®-based real-time PCR, and compared the results against women affected by preeclampsia.

RESULTS

All assessed miRNAs were detected in maternal plasma in pregnancies with and without preeclampsia. All except miR-222 were over-expressed during disease when compared to the second and to third-trimester controls. miR-20a, miR-21, miR-26a, and miR-223 were down-regulated in the third trimester in comparison to the second trimester in normal pregnancies.

CONCLUSION

The variation of the miRNAs expression through normal pregnancies suggested their involvement in normal physiological pregnancy processes. In contrast, the significant deregulation of the nine studied miRNAs during preeclampsia indicated the involvement of their target genes in the pathogenesis of the disease. miR-199a and miR-21-3p showed the greatest changes in expression. This study shows for the first time the presence of miR-20a, miR-199, and miR-424 and the variations they undergo in the plasma of pregnant women with preeclampsia.

摘要

背景

子痫前期是一种妊娠特有的综合征,其特征为高血压、蛋白尿和水肿。全球范围内,子痫前期影响2%至8%的妊娠,占孕产妇死亡的10%至15%。尽管其病因尚不清楚,但它包括涉及微小RNA(一种对靶mRNA具有转录后抑制作用的小非编码RNA分子)的复杂病理过程。

目的

为评估正常妊娠及合并子痫前期妊娠期间微小RNA的表达情况,对一组委内瑞拉女性进行了研究。

方法

在正常妊娠的孕中期和孕晚期,采用基于SYBR Green®的实时定量PCR法检测母体血浆中9种胎盘微小RNA(hsa-miR-20a-5p、21-3p、26a-5p、181a-5p、199a-5p、210-3p、222-5p、223-3p、424-3p),并将结果与子痫前期患者进行比较。

结果

在有或无子痫前期的妊娠中,母体血浆中均检测到所有评估的微小RNA。与孕中期和孕晚期对照组相比,除miR-222外,所有微小RNA在疾病期间均过度表达。在正常妊娠中,与孕中期相比,miR-20a、miR-21、miR-26a和miR-223在孕晚期下调。

结论

正常妊娠期间微小RNA表达的变化表明它们参与正常的生理妊娠过程。相反,子痫前期期间9种研究的微小RNA的显著失调表明其靶基因参与了该疾病的发病机制。miR-199a和miR-21-3p的表达变化最大。本研究首次显示了miR-20a、miR-199和miR-424的存在及其在子痫前期孕妇血浆中的变化情况。

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