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

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.

Decorin promotes apoptosis and autophagy via suppressing c-Met in HTR-8 trophoblasts

“…These contradictory findings have suggested that autophagy activity in trophoblasts might change at different stages of pathogenesis. The Akt/mTOR signaling pathway is critical for cell autophagy and several groups reported that suppression of this pathway contributes to increasing autophagy and cell apoptosis in trophoblasts (Yeh et al 2016, Zhang et al 2018, Chen et al 2019. Here, our results revealed that DCN promotes autophagy in HTR-8 cells, in accordance with previous findings that DCN is an autophagy inducer in endothelial cells (Buraschi et al 2013) and breast carcinoma cells (Neill et al 2014).…”

RNA-Seq reveals changes in human placental metabolism, transport and endocrinology across the first–second trimester transition

“…In particular, laminin LAMA1 was highly expressed in the first trimester, whereas LAMB3, LAMA2, LAMC3 were upregulated in the second trimester. Laminins have an important role during implantation ( Haouzi et al, 2011 ), maintenance of trophoblast stemness ( Kiyozumi et al, 2020 ) and EVT migration ( Zhang et al, 2018b ).…”

Knockdown of DDX46 inhibits trophoblast cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway in preeclampsia

“…Downregulation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in PE placenta inhibits human trophoblast cell proliferation, migration, and invasion via regulating the PI3K/ Akt/mTOR pathway [24]. Laminin (LN)-α5 downregulation is associated with PE placenta and impairs trophoblast cell viability and invasiveness through the PI3K/Akt/mTOR pathway, which could be a causative factor of PE pathogenesis [33]. Concerning the mechanism of the DDX46 function, we further discovered that knockdown of DDX46 caused significantly decrease in the expression levels of p-Akt and p-mTOR in trophoblast cells.…”