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

• Published in: Cellular physiology and biochemistry Vol. 51; no. 5; pp. 2030 - 2040
• Main Authors: Zhang, Xue Mei, Xiong, Xi, Tong, Chao, Li, Qin, Huang, Shuai, Li, Qing Shu, Liu, Ya Ming, Li, Hai Ying, Baker, Phillip, Shan, Nan, Qi, Hong Bo
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.12.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Angiogenesis; Breast cancer; Cell adhesion & migration; Deoxyribonucleic acid; DNA; DNA methylation; Extracellular matrix; Hypertension; Kinases; Laminin (LN)- α5; Mammals; Membranes; Original Paper; Pathogenesis; PI3K signaling pathway; Preeclampsia; Pregnancy; Proteins; Roles; Trophoblast; United States > US; China; Laminin (LN)- α5; Trophoblast; PI3K signaling pathway; Preeclampsia
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000495822

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.