Luizon Marcelo R, Conceição Izabela M C A, Viana-Mattioli Sarah, Caldeira-Dias Mayara, Cavalli Ricardo C, Sandrim Valeria C
Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Front Physiol. 2021 Sep 22;12:678184. doi: 10.3389/fphys.2021.678184. eCollection 2021.
MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using a PCR array in plasma collected between 20 and 25 weeks of gestation from pregnant women, who subsequently developed PE and those who remained healthy during pregnancy, randomly selected from a prospective cohort. Overall, 23 miRNAs had a fold change > 2.0 and were considered to be upregulated in plasma from pregnant women who subsequently developed PE, even before the onset of clinical symptoms of PE. However, only miR-204-5p was statistically significant ( = 0.0082). Experimentally validated interactions for the target genes of miR-204-5p extracted from miRTarBase were used in the gene set functional enrichment analysis to identify Reactome pathways. The network connecting the 37 target genes for miR-204-5p revealed pathways of known pathophysiological relevance during the early development of PE and included key genes related to PE, such as , and . We further depicted downstream targets of SIRT1 that are related to the vascular endothelial function or implicated in the pathophysiology of PE, namely, FOXO1, NFκB, HIF-1α, NOS3, and PPAR-γ. Our novel findings provide for circulating miRNAs upregulated in the second trimester on plasma from pregnant women who subsequently developed PE that is potentially related to the early development of PE, which may guide further studies focused on the validation of potential predictive biomarkers in PE.
微小RNA（miRNA）在子痫前期（PE）的病理生理学中起重要作用。然而，在妊娠中期这一对于识别PE预测生物标志物至关重要的时期，尚未分析循环miRNA的表达情况。因此，我们使用PCR阵列检测了84种循环miRNA在妊娠20至25周期间收集的孕妇血浆中的表达谱，这些孕妇随后发生了PE以及那些孕期保持健康的孕妇，她们是从前瞻性队列中随机选取的。总体而言，23种miRNA的变化倍数>2.0，被认为在随后发生PE的孕妇血浆中上调，甚至在PE临床症状出现之前。然而，只有miR-204-5p具有统计学意义（P = 0.0082）。从miRTarBase中提取的miR-204-5p靶基因的实验验证相互作用用于基因集功能富集分析以识别Reactome途径。连接miR-204-5p的37个靶基因的网络揭示了PE早期发育过程中已知病理生理相关性的途径，包括与PE相关的关键基因，如 、 和 。我们进一步描绘了与血管内皮功能相关或与PE病理生理学有关的SIRT1的下游靶标，即FOXO1、NFκB、HIF-1α、NOS3和PPAR-γ。我们的新发现为随后发生PE的孕妇血浆中妊娠中期上调的循环miRNA提供了信息，这些miRNA可能与PE的早期发育有关，这可能指导进一步研究聚焦于PE潜在预测生物标志物的验证。
