P–422 Acylglycerol Kinase is a new novel marker in preeclampsia

Abstract Study question What is the potential function of Acylglycerol Kinase (AGK) in the pathogenesis of preeclampsia(PE). Summary answer AGK plays an important role in the pathogenesis of PE by influencing the function of the trophoblast cells. What is known already PE is the leading cause of maternal and perinatal mortality and morbidity. The underlying mechanism is still not completely elucidated. Disorder migration, invasion and mitochondria function of trophoblast cells are one of mechanism in preeclampsia. AGK is a subunit of the mitochondrial channel protein complex TIM22, and maintain the stability of mitochondrial structure and function. Studies have shown that AGK is related to the development of various cancers by infecting the cells migration and invasion. It will be interesting to explore the potential function of AGK in the process of early trophoblast development and the pathogenesis of PE. Study design, size, duration Firstly, explore the expression of AGK in PE. Secondly, lentivirus systems was used to generate loss and gain of function models in trophoblast cell line-HTR8/Sneov to study the role of AGK in the pathogenesis of PE. Participants/materials, setting, methods We examined the expression of AGK both in placental tissues from PE patients and normal pregnant patients. Meanwhile, we generated AGK loss and gain of function models in HTR8/Sneov cells by using lentivirus systems. Transwell assays, scratch-wound assays, EDU and plate clone formation assays, cell apoptosis assays, cell cycle assays, ATP concentration, mtDNA level and transmission electron microscopy were used to examine the function of AGK in HTR8/Sneov cells model. Main results and the role of chance In this study, AGK was significantly decreased in the extra-villous trophoblast (EVT) cells in placental tissues of PE patients compared with that in control group by immunohistochemistry. And further confirmed the expression of AGK in placental tissues by QPCR, western blot. We demonstrated that knockdown of AGK in HTR8 dramatically decreased the cell proliferation, migration and invasion. It also showed the significantly lower plate clone formation rate in AGK knockdown -HTR8 cells compare with the WT HTR8 cells. While overexpression of AGK in HTR8 dramatically increased the cell proliferation, migration, invasion and higher plate clone formation rate. Further, we demonstrated that AGK regulated the ATP level and mtDNA level in HTR8 cells model. And we found that knockdown AGK decreased the number of mitochondria, and shown the mitochondrial crista disorder, mitochondrial swelling and dissolution and mitochondrial membrane fragmentation. While overexpression AGK increased the number of mitochondria. Limitations, reasons for caution Although we show that AGK played an important role in the function of HTR8, the study of working mechanism of AGK in PE is still very limited. More studies will be performed to explore its underline mechanism. Wider implications of the findings: This study was the first time to explore the role of AGK in PE. It will help us to better understand the pathogenesis of PE, which might be helpful in future application of novel therapeutic targets in PE. Trial registration number Not applicable