Apelin-36 alleviates LPS-induced trophoblast cell injury by inhibiting GRP78/ASK1/JNK signaling.

Pre-eclampsia (PE) is a type of hypertensive disorder of pregnancy that poses a serious threat to the health of both mother and fetus. Inhibition of the inflammatory environment on trophoblast cells is of great significance to improve PE. Apelin-36 is an endogenous active peptide with strong anti-inflammatory activity. Therefore, this study aims to investigate the effects of Apelin-36 on lipopolysaccharide (LPS)-induced trophoblast cells and its potential mechanism. The levels of inflammatory factors (TNF-α, IL-8, IL-6 and MCP-1) were detected by reverse transcription-quantitative PCR (RT-qPCR). The proliferation, apoptosis, migration and invasion capacities in trophoblast cells were detected by CCK-8, TUNEL staining, wound healing and Transwell assays, respectively. GRP78 was overexpressed by cell transfection. Western blot was applied for the identification of protein levels. Apelin concentration-dependently decreased the expression of inflammatory cytokines and p-p65 protein level in trophoblast cells induced by LPS. Apelin treatment reduced LPS-induced apoptosis and improved the proliferation, invasion and migration capacities of LPS-mediated trophoblast cells. Additionally, Apelin down-regulated GRP78, p-ASK1 and p-JNK protein levels. The inhibition on LPS-induced trophoblast cell apoptosis and the promotion on invasion and migration by Apelin-36 was counteracted by GRP78 overexpression. To sum up, Apelin-36 could alleviate LPS-induced cell inflammation and apoptosis and improve the invasion and migration of trophoblasts by inhibiting the GRP78/ASK1/JNK signaling.