MiR-142-5p mediated Nrf2 dysregulation in gestational diabetes mellitus and its impact on placental angiogenesis

IF 3 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Placenta Pub Date : 2024-10-24 DOI:10.1016/j.placenta.2024.10.021
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Abstract

Introduction

Gestational diabetes mellitus (GDM) presents significant risks during pregnancy, including adverse perinatal outcomes and placental dysfunction. Impaired angiogenesis, involving crucial factors like Vascular Endothelial Growth Factor (VEGF), contributes to these complications. The Nrf2/Keap1 pathway, crucial for vascular redox homeostasis, has been linked to GDM-associated angiogenesis dysregulation.

Methods

This study aimed to investigate the molecular mechanisms underlying placental Nrf2 regulation, focusing on angiomiRs, key regulators of angiogenesis in GDM. Computational analysis identified miR-142-5p targeting Nrf2 mRNA. Expression levels of miR-142-5p were assessed in GDM placenta and correlated with Nrf2 expression. Experimental validation utilized human trophoblastic cell lines (BeWo) exposed to hyperglycemic conditions, assessing the effects of anti-miR-142 transfection on Nrf2 expression and angiogenic marker levels.

Results

miR-142-5p expression was significantly downregulated in GDM placenta, correlating positively with Nrf2 expression. In BeWo cells exposed to hyperglycemia, anti-miR-142 transfection notably increased Nrf2 expression alongside angiogenic marker levels, confirming the computational predictions.

Discussion

Our findings highlight the pivotal role of miRNAs in GDM-associated impaired angiogenesis by modulating Nrf2 expression. Understanding these molecular mechanisms provides insights into potential therapeutic targets for improving pregnancy outcomes in GDM cases.
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妊娠期糖尿病中 MiR-142-5p 介导的 Nrf2 失调及其对胎盘血管生成的影响
导言:妊娠期糖尿病(GDM)在妊娠期间具有重大风险,包括不利的围产期结局和胎盘功能障碍。血管生成受损,血管内皮生长因子(VEGF)等关键因子参与其中,是导致这些并发症的原因之一。Nrf2/Keap1通路对血管氧化还原平衡至关重要,它与GDM相关的血管生成失调有关:本研究旨在研究胎盘Nrf2调控的分子机制,重点关注GDM中血管生成的关键调控因子--angiomiRs。计算分析发现了靶向 Nrf2 mRNA 的 miR-142-5p。评估了 miR-142-5p 在 GDM 胎盘中的表达水平,并将其与 Nrf2 的表达相关联。实验验证利用暴露于高血糖条件下的人类滋养细胞系(BeWo),评估抗 miR-142 转染对 Nrf2 表达和血管生成标志物水平的影响。在暴露于高血糖的 BeWo 细胞中,抗 miR-142 转染明显增加了 Nrf2 表达和血管生成标志物水平,证实了计算预测:我们的研究结果凸显了 miRNA 通过调节 Nrf2 表达在 GDM 相关血管生成障碍中的关键作用。通过了解这些分子机制,我们可以深入了解改善 GDM 妊娠结局的潜在治疗靶点。
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来源期刊
Placenta
Placenta 医学-发育生物学
CiteScore
6.30
自引率
10.50%
发文量
391
审稿时长
78 days
期刊介绍: Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
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