Abstract
Preeclampsia (PE), a hypertensive complication in pregnancy, is a major contributor to maternal and fetal morbidity and mortality. PE has long been regarded a heterogeneous disorder with a pathogenesis that involves multiple genes and factors. Glucose transporter 1 (GLUT1) is a central rate-limiting pump that is involved in glucose uptake and subsequent utilization. Our previous RNA-seq results demonstrated GLUT1 was significantly downregulated in deciduas from patients with severe PE. Therefore, in this study, we aimed to explore the role of GLUT1 in the occurrence of PE. Our data showed that mRNA and protein levels of GLUT1 were significantly downregulated in the deciduas from patients with severe PE. Additionally, GLUT1 levels were substantially upregulated in human endometrial stromal cells (HESCs) during in vitro decidualization. Moreover, GLUT1 knockdown significantly reduced the mRNA levels of decidualization markers (IGFBP1 and PRL) and aerobic glycolysis-related genes (LDHA and MCT4), as well as decreased glucose uptake and lactate production. Furthermore, upon GLUT1 knockdown, the levels of apoptotic genes P53, P21, and BAX increased whereas the level of BCL2 decreased. Target prediction results and luciferase analysis showed that GLUT1 is one of the targets of miR-140-5p, which is partly responsible for downregulated GLUT1 levels. Collectively, these results demonstrate that GLUT1 exerts a pivotal role in human decidualization by participating in glycolysis, and that GLUT1 deficiency may trigger aberrant glycolysis, thereby leading to destructive decidualization that may impede blastocyst implantation, trophoblast invasion, and subsequent placental development, which are associated with PE. Taken together, these data suggest that GLUT1 might be a promising target for PE therapy.
Highlights
Preeclampsia (PE) is an obstetric disorder affecting 5–10% of all pregnancies worldwide, especially in developing countries, and it is a major contributor to considerable maternal and perinatal morbidity and mortality [1]
Severe proteinuria was detected in Severe PE (sPE) group, whereas normal pregnant women had no signs of proteinuria
We conclude that Glucose transporter 1 (GLUT1) which is affected by aberrant miRNA is an important player in decidualization through participating in glycolysis, and its deficiency may attenuate glycolysis and cause suboptimal decidual response, which is possibly related to PE
Summary
Preeclampsia (PE) is an obstetric disorder affecting 5–10% of all pregnancies worldwide, especially in developing countries, and it is a major contributor to considerable maternal and perinatal morbidity and mortality [1]. The precisely synchronous development of the “seed”, an adequate embryo, and the “soil”, decidua is a prerequisite for embryo implantation, placentation and pregnancy maintenance[10]. Our recent studies highlight the causative role of the abnormal decidualization in the progression of PE [11,12,13], and this view has been confirmed by other researches [14, 15]. Preeclampsia (PE), a hypertensive complication in pregnancy, is a major contributor to maternal and fetal morbidity and mortality. We aimed to explore the role of GLUT1 in the occurrence of PE
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