AXL Deficiency Affects Trophoblast Invasion And Spiral Arterial Remodeling In The Onset Of Preeclampsia

Preeclampsia is a human-specific pregnancy syndrome that affects 3%-5% of primiparas and is the leading cause of maternal and perinatal mortality and morbidity worldwide.Clinically,the maternal emerge high blood pressure,proteinuria and other symptoms after 20 weeks of pregnancy,while the fetus is characterized by premature birth,intrauterine growth restriction,placental abruption and death.In addition,mothers and children are inclined to be affected by long-term cardiovascular complications.Studies on preeclampsia continue to deepen,while the precise pathogenesis of preeclampsia is still poorly understood.A large number of previous studies have confirmed that the symptoms of preeclampsia will be fading away with the stripping of placental tissue during delivery,it reveals that the placenta under pathological conditions may be the leading cause for the pathogenesis of PE.In addition,it was confirmed that inadequate trophoblast invasion and abnormal spiral artery remodeling will cause abnormal placentation and fetal development.It reveals that the placenta under pathological conditions plays a vital role in the pathogenesis of preeclampsia.AXL is a member of TAM receptor tyrosine kinase family(TYRO3-AXL-MER)and is widely expressed in the body,such as platelets,heart,skeletal muscle,liver,kidney and so on.The ligand GAS6 binding to AXL and activates tyrosine kinase activity.It plays an important role in cell adhesion,anti-apoptosis,proliferation and migration by activating downstream signal transduction pathways.Recent studies have found that AXL is highly expressed in a variety of tumor tissues,and activation of the GAS6/AXL signaling pathway plays an important role in tumor cell invasion,metastasis,and angiogenesis.It is also having some research in the field of reproduction,but these researches on AXL about preeclampsia are controversial and incomplete.In this research,we based on the similar between trophoblast cell and tumor cell during placentation and tumorigenesis to speculate that the deficiency of AXL may affect trophoblast invasion and spiral artery remodeling trigger preeclampsia.Through the study use of AXL knockout mice,it was found that the deficiency of AXL can cause symptoms similar to preeclampsia in the middle of pregnancy,reduced placental weight,and intrauterine growth restriction.Further research found that the abnormal development of placenta and spiral artery remodeling in AXL knockout mice.In vitro trophoblast cell invasion experiments and tube formation experiments also confirmed that the deficiency of AXL can affect trophoblast cell invasion and tube formation.In summary,we conclusion that AXL plays an important role in pregnancy.The absence of AXL will cause inadequate trophoblast invasion and insufficient spiral artery remodeling trigger preeclampsia.