Activation of the ERK1/2 signaling pathway enhances proliferation and apoptosis of trophoblast in preeclampsia rats

Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):598-604. doi: 10.26355/eurrev_202101_24617.

Abstract

Objective: The aim of this study was to investigate the influences of the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway on preeclampsia rats as well as the proliferation and apoptosis of trophoblasts.

Materials and methods: A proper number of conceived rats were applied to prepare the preeclampsia model (group P). Meanwhile, others were enrolled as control group (group C). The differences in placental structure between the two groups were compared via hematoxylin-eosin (HE) staining. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were compared between the two groups as well. In addition, T25 cell lines were divided into three groups, including Control group, hypoxia/reoxygenation (H/R) group and H/R + Staurosporine group (an activator of the ERK1/2 signaling pathway). The protein expression of phosphorylated (p)-ERK1/2 in the aforementioned model groups and cells was detected through Western blotting. Cell apoptosis rate was determined by a flow cytometer. Moreover, methyl thiazolyl tetrazolium was utilized to measure the proliferative capacity of trophoblasts in the three groups. Transwell chamber assay was adopted to count the transmembrane cells.

Results: The cells in group P were arranged disorderly. Group P had remarkably lower SOD activity but higher MDA content than group C (p<0.05). The protein expression levels of ERK1/2 and p-ERK1/2 in the placenta of group C were evidently higher than those of group P (p<0.05). Besides, the protein expression levels of ERK1/2 and p-ERK1/2 were markedly up-regulated in Control group when compared with H/R + Staurosporine group, with the lowest in H/R group (p<0.05). The proliferative capacity of cells was gradually enhanced in the three groups with the increase of culture time. Cell proliferation was the strongest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05). The apoptosis and death rates of cells were the highest in H/R group, followed by H/R + Staurosporine group and Control group (p<0.05). However, the number of transmembrane cells was the largest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05).

Conclusions: The ERK1/2 signaling pathway is associated with preeclampsia in rats, whose activation can enhance cell proliferation and weaken cell apoptosis.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • MAP Kinase Signaling System
  • Male
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Rats
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology