基于RNA测序对高血压妊娠子代内皮细胞中差异表达微小RNA的分析:一项初步研究。
RNA sequencing-based profiling of differentially expressed microRNAs in endothelial cells from offspring of hypertensive pregnancies: a preliminary study.
作者信息
Mohd Isa Nurul Iffah, Abdull Sukor Aslah Nabilah, Syafruddin Saiful Effendi, Ahmad Mohd Faizal, Zainal Abidin Shahidee, Mokhtar Mohd Helmy, Ugusman Azizah, Hamid Adila A
机构信息
Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Faculty of Medicine, Universiti Teknologi Mara, Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, Malaysia.
出版信息
Front Mol Biosci. 2025 Jul 21;12:1520101. doi: 10.3389/fmolb.2025.1520101. eCollection 2025.
Offspring of mothers with hypertensive disorders of pregnancy (HDP) are at increased risk of developing endothelial dysfunction and cardiovascular disease (CVD) in adulthood. MicroRNAs (miRNAs), as key regulators of endothelial cells, may contribute to the early onset of endothelial dysfunction. However, there are limited studies characterizing the miRNA profile of endothelial cells in offspring of HDP. Therefore, this study aims to determine the miRNA expression profile of human umbilical vein endothelial cells (HUVECs) isolated from the offspring of HDP. HUVECs were obtained from both normal and hypertensive umbilical cords. RNA sequencing analysis revealed that eight miRNAs were significantly upregulated in HUVECs from HDP (p < 0.05). The target genes of these miRNAs were then predicted using four databases: miRDB, TargetScan, DIANA-microT-CDS, and miRWalk. Gene ontology, pathway enrichment, and protein-protein interaction network analyses revealed that the target genes of these miRNAs are involved in cellular functions and pathways related to angiogenesis and cellular senescence, which may contribute to endothelial dysfunction and CVD. The most significantly upregulated miRNA, hsa-miR-196a-5p expression was then validated through stem-loop RT-qPCR where its expression was significantly upregulated in hypertensive HUVEC by 6-fold as compared to normal HUVEC (p < 0.01). These findings offer insights into the role of miRNAs in the development of CVD in offspring exposed to HDP, highlighting their potential as predictive markers and therapeutic targets in the future.
患有妊娠高血压疾病(HDP)的母亲的后代在成年后患内皮功能障碍和心血管疾病(CVD)的风险增加。微小RNA(miRNA)作为内皮细胞的关键调节因子,可能促成内皮功能障碍的早期发生。然而,关于HDP后代内皮细胞miRNA谱特征的研究有限。因此,本研究旨在确定从HDP后代分离的人脐静脉内皮细胞(HUVEC)的miRNA表达谱。HUVEC取自正常和高血压脐带。RNA测序分析显示,HDP来源的HUVEC中有8种miRNA显著上调(p<0.05)。然后使用四个数据库(miRDB、TargetScan、DIANA-microT-CDS和miRWalk)预测这些miRNA的靶基因。基因本体论、通路富集和蛋白质-蛋白质相互作用网络分析显示,这些miRNA的靶基因参与了与血管生成和细胞衰老相关的细胞功能和通路,这可能导致内皮功能障碍和CVD。然后通过茎环RT-qPCR验证了上调最显著的miRNA,即hsa-miR-196a-5p的表达;与正常HUVEC相比,其在高血压HUVEC中的表达显著上调了6倍(p<0.01)。这些发现为miRNA在暴露于HDP的后代CVD发生中的作用提供了见解,突出了它们未来作为预测标志物和治疗靶点的潜力。
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