Upregulation of SEMP1 Contributes to Improving the Biological Functions of Trophoblast via the PI3K/AKT Pathway in Preeclampsia

• Published in: Molecular biotechnology 2024-03, Vol.66 (3), p.531-543
• Main Authors: Chang, Ruijing, Su, Yuan, Kong, Hongfang, Wang, Fang, Xing, Ying, Jiang, Lei, Xin, Hong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Arginine; Arteries; Biochemistry; Biological Techniques; Biotechnology; Cell Biology; Cell migration; Cell proliferation; Chemistry; Chemistry and Materials Science; Cytokeratin; Endothelial cells; Gene expression; Growth factors; Human Genetics; Hypertension; Membrane proteins; Membranes; NG-Nitroarginine methyl ester; Original Article; Placenta; Pre-eclampsia; Preeclampsia; Pregnancy complications; Protein Science; Proteins; Proteinuria; Senescence; Signal transduction; Umbilical vein; Vascular endothelial growth factor
• ISSN: 1073-6085; 1559-0305
• DOI: 10.1007/s12033-023-00774-3

Disturbance of extravillous trophoblast infiltration is associated with preeclampsia (PE), a severe condition of pregnancy characterized by hypertension and proteinuria. Senescence-associated epithelial membrane protein 1 (SEMP1), an integral membrane protein, is a vital component of tight junction strands in epithelial or endothelial cells, with no clear function reported in PE. Gene Expression Omnibus (GEO) datasets showed that SEMP1 expression was downregulated in the placental tissues of PE patients, which was confirmed by assessing SEMP1 levels in placental samples collected in our hospital. Furthermore, less SEMP1 was detected in cytokeratin 7 positive trophoblast cells in the spiral arteries of rat placentas post L-arginine methyl ester hydrochloride (L-NAME) treatment. Trophoblast cells acquired robust ability of proliferation, migration, and invasion when SEMP1 was overexpressed. Such capability was weakened in SEMP1-silenced cells. Trophoblast cells overexpressing SEMP1 secreted more vascular endothelial growth factor A (VEGFA), which facilitated the tube formation of human umbilical vein endothelial cells. Blockade of PI3K/AKT signaling transduction with LY294002 dampened the effects of SEMP1 on trophoblast cells. Collectively, we firstly indicated that SEMP1 inhibition is a potential driver for PE, which may be associated with the deactivation of the PI3K/AKT pathway. Graphical Abstract SEMP1 was involved in PE progression by regulating cell growth, migration, invasion, and tube formation via PI3K/AKT signaling pathway in trophoblast cells and endothelial cells.