| BackgroundPreeclampsia(PE)is a specific pregnancy syndrome with an incidence of 3-8%and is characterized by edema,hypertension,and proteinuria after 20 weeks of gestation.Diagnosis of preeclampsia can be challenging because there are often no obvious symptoms in early pregnancy.In addition to termination of pregnancy,there is currently no effective treatment,which easily leads to the risk of fetal preterm birth,and preeclampsia is a high risk factor for permanent cardiovascular damage and physical decline in pregnant women and their offspring[1-2].With the opening of threechild policy today,the probability of PE in older women has been greatly increased.Clarifying the pathogenesis of PE has become an urgent problem to be solved,providing a new perspective and target for the early diagnosis and treatment of PE and improving the prognosis,aiming at reducing the risk of PE in pregnant women and improving the quality of the population from the source.Objective1.To construct a prospective case-control study to analyze the relationship between serum IGFBP2 before 20 weeks of gestation and high risk factors,adverse outcomes,severity and clinical laboratory indicators of preeclampsia,and to investigate the diagnostic and predictive value of serum IGFBP2 for preeclampsia.2.To study the correlation between the expression of IGFBP2 in serum and placental tissue and preeclampsia;3.To study the effects of IFGFBP2 on the apoptosis,invasion and proliferation of placental trophoblast cells;4.To explore the potential molecular mechanism of IGFBP2 involvement in preeclampsia.MethodsThe potential marker IGFBP2 in the serum of pregnant women with preeclampsia was screened by protein microarray and mass spectrometry proteomics,and then verified by ELISA and immunohistochemistry.IGFBP2 combined with high risk factors and routine blood indicators were used to predict the onset of preeclampsia,and a regression analysis model was obtained.To observe the effects of IGFBP2 overexpression and silencing on the invasion,proliferation and apoptosis of placental trophoblast cells.Finally,immunofluorescence,immunoprecipitation and Western blotting were used to explore the molecular mechanism of IGFBP2 involved in the development of preeclampsia,and whether IGFBP2 affected Wnt/β-catenin pathway and its downstream proteins by interacting with DDK1.Results1.The occurrence of preeclampsia is affected by many high risk factors,which can produce adverse maternal and infant outcomes.The changes of clinical indicators suggest the early occurrence of preeclampsia.2.Serum levels of IGFBP2 in PE group were significantly lower than those in normal pregnancy group by protein microarray,mass spectrometry and ELISA.This result was confirmed in placental tissue of pregnant women in early pregnancy,indicating that IGFBP2 may be a potential marker of preeclampsia.The regression analysis model of serum IGFBP2 combined with high risk factors and routine blood indicators before 20 weeks of pregnancy for predicting preeclampsia was obtained:Y=18.841-0.085*(IGFBP2)+0.630*(RDW)+0.165*(AST)+0.863(MPV).3.The up-regulation of IGFBP2 promoted the proliferation and invasion of HTR8/SVneo cells.On the contrary,the down-regulation of IGFBP2 could inhibit the proliferation and invasion of HTR-8/SVneo cells.IGFBP2 expression has no significant effect on the apoptosis and proliferation of HTR-8/SVneo cells in preeclampsia.4.IGFBP2 regulates Wnt/β-catenin signaling pathway by interacting with DKK1,and affects the changes of MMP2 and MMP9 proteins related to invasion and proliferation downstream of the pathway.Conclusion1.Serum IGFBP2 before 20 weeks of gestation combined with high risk factors and routine blood indicators has a high early predictive value for preeclampsia.2.Decreased IGFBP2 level can inhibit the proliferation and invas ion of placental trophoblast cells.3.IGFBP2 regulates Wnt/β-catenin signaling pathway by interacting with DKK1,and affects the changes of MMP2 and MMP9 proteins related to invasion and proliferation downstream of the pathway. |
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