Levels of microRNA-181b and plasminogen activator inhibitor-1 are associated with hypertensive disorders complicating pregnancy.

Yan-Shan Chen,Ying Wang,Ling Shen,Rui-Qin Mai

doi:10.3892/etm.2014.1946

Abstract

The aim of the present study was to explore the association between the expression of microRNA (miRNA)-181b and plasminogen activator inhibitor-1 (PAI-1) in the placental tissue of pregnant females with a hypertensive disorder complicating pregnancy (HDCP). Placental tissue samples were obtained from 48 patients with HDCP and 40 females with a normal pregnancy. The levels of miRNA-181b and PAI-1 mRNA were determined by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of PAI-1 protein was analyzed by western blotting. Vascular smooth muscle cells (VSMCs) were transfected with the pEGP-miRNA-181b plasmid using Lipofectamine® 2000. Transfection efficiency was confirmed by immunohistochemical analysis. The levels of miRNA-181b in the placental tissue of patients with HDCP were lower than those in the control group, whereas the levels of PAI-1 mRNA in the placental tissue of patients with HDCP were higher than those in the control group. The expression of the PAI-1 protein in the HDCP group was higher than that in the control group. Following transfection of VSMCs with plasmid pGCMV/EGFP/miRNA-181b, the levels of PAI-1 mRNA were reduced while the levels of miRNA-181 were upregulated. Furthermore, the expression levels of PAI-1 protein were lower than those in the control group. The levels of miRNA-181b and PAI-1 mRNA were strongly associated with HDCP. Thus, miRNA-181b may play an important role in the regulation of PAI-1. PAI-1 and miRNA-181b may be novel biomarkers to be used in HDCP therapy.

Highlights

Hypertensive disorder complicating pregnancy (HDCP) is a common clinical obstetric complication with an incidence rate of 5% in China [1]
The results revealed that the level of miRNA‐181b in the placental tissue from the HDCP group was significantly lower than that in the placental tissue from the control group (P
The levels of Plasminogen activator inhibitor‐1 (PAI‐1) mRNA in the placental tissue from patients with gestational hypertension, mild pre‐eclampsia and severe pre‐eclampsia increased 1.98, 2.79- and 5.8‐fold, respectively, compared with those from the control group (Fig. 1B). These data indicated that HDCP reduced the levels of miRNA‐181b but increased the levels of PAI‐1 mRNA in placental tissue

Summary

Introduction

Hypertensive disorder complicating pregnancy (HDCP) is a common clinical obstetric complication with an incidence rate of 5% in China [1]. MicroRNA (miRNA)‐181b, a member of the miRNA‐181 family, has been revealed to be involved in the proliferation, invasion and apoptosis of tumor cells that are associated with tumor invasiveness [2,3]. Previous studies on the pathological mechanisms of HDCP have demonstrated that the placenta plays an important role in the occurrence and development of HDCP; the mechanism is associated with the reduced invasiveness of trophoblastic cells and pathological changes in small branches of the main uterine artery [7,8]. Studies have indicated that miRNA‐181 has an effect on the proliferation of cells, the regulation of angiogenesis, the conditioning of the immune system [10], tumor invasion and apoptosis [11]. MiRNA‐181b has been demonstrated to promote the proliferation and invasiveness of multiple tumor cells and is closely associated with tumor apoptosis [14]. The effect of miRNA‐181b on the occurrence and development of HDCP has not, to the best of our knowledge, been previously studied

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