miRNA-141-5p Affects the Levels of Neutrophil Elastase in Preeclampsia by Regulating MAPK1.

Objective: The objective of this study was to investigate the expression levels of microRNA-141-5p(miRNA-141-5p), MAPK1 and neutrophil elastase in patients with and without preeclampsia (PE), and the relationship between miRNA-141-5p and MAPK1 with respect to the secretion of elastase by neutrophils in patients with PE.

Methods: Thirty patients with PE and 30 healthy pregnant (HP) women were recruited from The Second Hospital of Shanxi Medical University, Taiyuan, China, between February 2017 and July 2018. Neutrophils were isolated from 8 mL peripheral blood samples and cultured. We recorded neutrophil count and morphology during culture. Apoptosis was detected by flow cytometry in different groups at 0, 24, and 48 h. The expression levels of elastase were detected in neutrophils by enzyme-linked immunosorbent assay, whereas the expression levels of miRNA-141-5p in peripheral blood neutrophils were detected by real-time polymerase chain reaction. We used TargetScanHuman Release 7.2 to analyze the target genes of miRNA-141-5p. The expression of MAPK1 in peripheral blood neutrophils was detected by western blotting. Data were analyzed by SPSS version 21.0 software, and comparisons between groups were carried out with the Student test.

Results: There was no significant difference between the PE and HP groups ( > 0.050) with regard to age or body mass index. The weight of newborns in the PE group (2846.00 ± 600.00 g) was significantly lower than that in the HP group (3055.00 ± 230.68 g). The number of neutrophilic granulocytes(NGs) in blood samples from the PE group was significantly higher than that in the HP group ( = 0.003). There was no significant difference between the groups with regard to morphology. Apoptosis in the PE group was delayed when compared with the HP group at different time points. The value of apoptosis in the PE and HP groups were respectively 0.790, < 0.001 and 0.030 at 0 h, 24 h and 48 h. The expression levels of miRNA-141-5p in the PE group were significantly lower than those in the HP group ( < 0.050). The expression levels of MAPK1 in neutrophils from the PE group were significantly higher than those in the HP group ( < 0.050) by western blot. The expression levels of elastase in neutrophils from the PE group were significantly higher than those in the HP group ( < 0.050). Furthermore, the number of NGs in peripheral blood from the PE group was higher than that of the HP group; however, the levels of apoptosis were lower. The expression levels of miRNA-141-5p in NGs decreased, the expression of MAPK1 increased, and the secretion of neutrophil elastase in the NG medium increased in the PE group than those in the HP group.

Conclusion: Collectively, our analysis suggested that miRNA-141-5p may be involved in the pathogenesis of PE by regulating the MAPK1 signaling pathway to activate neutrophils and increase the secretion of elastase.