Abstract
Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.
Highlights
Preeclampsia (PE) is a pregnancy-associated disorder, which affects 3–5% of pregnancies, and is characterized by hypertension and proteinuria, which develops after 20 weeks of gestation in women [1]
Excessive trophoblast cell apoptosis and superficial trophoblast invasion leading to insufficient spiral artery remodeling and placental hypoxia are associated in the pathogenesis of PE [4,5]
The results showed that miR-183 expression markedly up-regulated in the serum and placental tissues of PE pregnancies compared with that normal pregnancies (Figure 1B,C; P
Summary
Preeclampsia (PE) is a pregnancy-associated disorder, which affects 3–5% of pregnancies, and is characterized by hypertension and proteinuria, which develops after 20 weeks of gestation in women [1]. According to American College of Obstetricians and Gynecologists (ACOG), PE is categorized into mild and severe. Severe PE is categorized as severe if systolic blood pressure (BP) is 160 mmHg or higher, diastolic BP of 110 mmHg or higher in two random urine samples, with either evidence of mild proteinuria, or mild hypertension plus severe proteinuria [2]. Severe PE, whether mild or, can develop into eclampsia, maternal multiorgan damage and death [3]. Excessive trophoblast cell apoptosis and superficial trophoblast invasion leading to insufficient spiral artery remodeling and placental hypoxia are associated in the pathogenesis of PE [4,5]. Many molecular mechanisms have been revealed, but the role of microRNAs (miRNAs) in the trophoblast dysfunction seen in PE remains to be elucidated
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