Background: Preeclampsia (PE), a hypertensive complication in pregnancy, is a major contributor to maternal and fetal morbidity and mortality. Thus far, the molecular mechanism underlying PE has not been investigated thoroughly. Glucose transporter 1 (GLUT1) is a central rate-limiting pump for glucose uptake and subsequent utilization. Our previous RNA-seq results demonstrated it was significantly downregulated in deciduas from severe PE patients. Therefore, we aimed to explore the role of GLUT1 in the occurrence of PE.Methods: In this study, GLUT1 levels were evaluated by quantitative PCR, Western blotting and immunohistochemical staining in severe preeclamptic deciduas. The levels of GLUT1 during decidualization were also studied in human endometrial stromal cells (hESCs). Moreover, the role of GLUT1 during decidualization was studied by GLUT1-siRNA treatment. Furthermore, we explored the regulatory role of miRNA in GLUT1 expression.Results: The expression of GLUT1 was significantly downregulated in the deciduas from severe PE patients. Additionally, the level of GLUT1 was substantially induced in 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), and decreased glucose uptake and lactate production. Furthermore, the levels of apoptotic genes P53, P21 and BAX increased whereas the levels of BCL2 decreased after GLUT1 knockdown. Target prediction results and luciferase analysis showed GLUT1 is one of the targets of miR-140-5p, which is partly responsible for the impaired GLUT1 level. Conclusion: These results demonstrate that GLUT1 exerts pivotal role in human decidualization by participating in glycolysis, and its deficiency may trigger aberrant glycolysis and thus leads to destructive decidualization, which may be a pathogenetic mechanism of PE. These data suggest GLUT1 might be a promising target for PE therapy.
