Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway

Cell Physiol Biochem. 2018;51(5):2030-2040. doi: 10.1159/000495822. Epub 2018 Dec 6.

Abstract

Background/aims: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion.

Methods: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP).

Results: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas.

Conclusion: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.

Keywords: Laminin (LN)- α5; PI3K signaling pathway; Preeclampsia; Trophoblast.

MeSH terms

  • Adult
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • DNA Methylation
  • Down-Regulation*
  • Female
  • Humans
  • Laminin / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Signal Transduction*
  • Trophoblasts / cytology
  • Trophoblasts / metabolism
  • Trophoblasts / pathology*

Substances

  • Laminin
  • laminin alpha5
  • Phosphatidylinositol 3-Kinases