Leukemia inhibitory factor promote trophoblast invasion via Urokinase-type plasminogen activator receptor in preeclampsia

• 1、department of biochemistry and molecular biology,dalian

Abstract：Preeclampsia is a pregnancy-related syndrome which could cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remain unclear. In current study, we found that the level of uPAR is relatively lower in the placentas form preeclamptic patients as compared with normal pregnancies women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced trophoblast cell lines (JAR and JEG-3 cells) migration and invasion potential through uPAR, and with increased gelatinolytic activities of matrix metalloproteinase 9. The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data support a role of LIF in promoting trophoblast migration/invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia.

Keywords： LIF uPAR preeclampsia trophoblast invasion PI3K/Akt