Milan K L, Gayatri V, Kriya Kumaran, Sanjushree N, Vishwanathan Palanivel Sri, Anuradha M, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, 603 203, Tamil Nadu, India.
Department of Obstetrics & Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur, 603203, Tamil Nadu, India.
Placenta. 2024 Dec;158:192-199. doi: 10.1016/j.placenta.2024.10.021. Epub 2024 Oct 24.
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.
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.
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.
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.
妊娠期糖尿病（GDM）在孕期会带来重大风险，包括不良围产期结局和胎盘功能障碍。血管生成受损，涉及血管内皮生长因子（VEGF）等关键因素，会导致这些并发症。对血管氧化还原稳态至关重要的Nrf2/Keap1通路，已与GDM相关的血管生成失调有关。
本研究旨在探讨胎盘Nrf2调控的分子机制，重点关注血管生成微RNA（angiomiRs），即GDM血管生成的关键调节因子。通过计算分析确定了靶向Nrf2 mRNA的miR-142-5p。评估了GDM胎盘组织中miR-142-5p的表达水平，并将其与Nrf2的表达进行关联分析。实验验证采用暴露于高血糖条件下的人滋养层细胞系（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。
GDM胎盘组织中miR-142-5p的表达显著下调，与Nrf2的表达呈正相关。在暴露于高血糖的BeWo细胞中，抗miR-142转染显著增加了Nrf2的表达以及血管生成标志物的水平，证实了计算预测结果。
我们的研究结果突出了微小RNA（miRNAs）通过调节Nrf2表达在GDM相关血管生成受损中所起的关键作用。了解这些分子机制有助于深入了解改善GDM患者妊娠结局的潜在治疗靶点。
