Abstract
Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.
Highlights
Preeclampsia (PE) is a pregnancy specific multisystem hypertensive disorder that affects 3–5% of pregnancies, a major contributor to maternal, neonatal morbidity and mortality (Mol et al, 2016)
Theses parameters were significantly different among ePE and eCON, ePE, and lCON groups respectively (P < 0.05), which might demonstrate the feature of early-onset preeclampsia
(4) Urine acidity and Hematokrit were significantly different between lPE and lCON (P < 0.05) without differences between ePE and CON which might be involved in the different pathogenesis of lateonset preeclampsia
Summary
Preeclampsia (PE) is a pregnancy specific multisystem hypertensive disorder that affects 3–5% of pregnancies, a major contributor to maternal, neonatal morbidity and mortality (Mol et al, 2016). Termination of pregnancy is still the only effective treatment which induces iatrogenic preterm birth and adverse maternal and fetal outcomes. Cytotrophoblasts translocate from the chorionic villi into the uterus endometrium, achieving the inner third of the myometrium. Cytotrophoblasts invade deeply the spiral arteries to replace the lining of maternal endothelia and interpose themselves amongst the vascular smooth muscle cells. The invasion of cytotrophoblasts is frequently shallow and incomplete in preeclampsia. The insufficient trophoblast invasion in first stage causes placental ischemia and hypoxia, the released damaging factors effecting on systemic vascular endothelial cell induces the clinical symptoms in the second stage (Fisher, 2015). The main investigative focus is the initial stage of the disease-trophoblast invasion disorder
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