Expression Of IFI16 In Placental Tissue And Serum Of Women With Preeclampsia And Its Relationship With The Pathogenesis Of Preeclampsia

Preeclampsia(PE)is one of the pregnancy-specific syndrome,which characterized by new-onset and persistent high blood pressure and associated with significant proteinuria after 20 weeks of pregnancy.The incidence of PE is 3-8% in the world,which seriously affect the maternal and child health.However,the exact pathogenesis of PE remains unknown.Now studies suggest that endothelial dysfunction is the central link in the pathogenesis of preeclampsia.Interferon-inducible protein 16(IFI16)is a member of the HIN200 family,which mainly located in the nucleus or cytoplasm of fibroblasts,hematopoietic cells,epithelial cells,endothelial cells,and trophoblastic cells.Recently,IFI16 was detected in the serum of patients with systemic autoimmune diseases,and high IFI16 levels may be associated with endothelial dysfunction.Oxidative stress,various pro-inflammatory cytokines,and cell density can trigger the expression of IFI16.Given that PE is in a state of potent oxidative stress and highly inflammatory response,furthermore,endothelial dysfunction is the predominant feature of PE,speculating IFI16 may be associated with the pathogenesis of PE.However,there are few reports about the role of IFI16 in PE.ObjectiveThis study explore the role of IFI16 in the pathogenesis of PE through detecting IFI16 expression in placental tissues and serum of women with preeclampsia,and analysing the correlation between serum IFI16 level with clinical indicators related with endothelial dysfunction,such as blood pressure,24-hour urine protein,serum total protein,albumin,urea,uric acid,creatinine,Cystatin c,?2-microglobulin,?1-microglobulin,lactate dehydrogenase and endothelin-1(ET-1),and finally,ROC curve and Youden index was used to judge the values of serum IFI16 levels in predicting PE,so as to discussion the relationship between IFI16 and PE pathogenesis,and provide laboratory evidence for clinical application of the indicator.MethodsPlacenta tissues and venous blood samples were obtained from women with PE and those with a normal pregnancy.IFI16 expression in placentas was evaluated by immunohistochemistry,western blot and real-time PCR.Serum total protein,albumin,urea,uric acid,creatinine,Cystatin c,?2-microglobulin,?1-microglobulin,lactate dehydrogenase,ET-1 and 24-hour urine protein of two groups were detected using an automatic biochemical analyzer.The serum levels of IFI16 and ET-1 were measured by ELISA.Then,the correlations between serum IFI16 levels with these clinical indicators were analyzed.SPSS 21.0 statistical software was applied for data analysis and processing,and the results were expressed as mean ± standard deviation.The independent samples t-test and Chi-square(?2)were used for comparison between the two groups;Correlation analysis using Pearson correlation test.ROC is used to judge whether IFI16 level can be used as a novel biological markers for predicting the occurrence of preeclampsia,and determine the corresponding forecast values.?=0.05 was used as the test standards.Results 1 General clinical data and detection index of two groups of pregnant women 1.1 Comparison of general clinical data between the two groups of pregnant womenThe average age of PE group and control group were(30.9 ± 4.6)years and(29.2 ± 4.2)years respectively,gestational age at sampling were(34.2 ± 2.3)weeks and(34.3 ± 1.0)weeks respectively,gestational age of delivery were(35.3 ± 2.6)weeks and(38.6 ± 1.0)weeks respectively,systolic blood pressure were(156.6±9.6)mmHg and(115.1±9.5)mmHg respectively,diastolic blood pressure were(103.9±7.6)mmHg and(73.6±5.9)mmHg respectively,fetal weights were(2170.3 ± 309.2)g and(3316.1 ± 456.1)g respectively,24-hour proteinuria were(2003.5±110.9)mg and(83.2±17.2)mg respectively.After statistical analysis,the differences of average age and gestational age at sampling in two group were not statistically significant(P>0.05).Preeclampsia group Systolic blood pressure,diastolic blood pressure and 24-hour proteinuria in PE group were higher than those in the control group(P<0.05).Gestational age of delivery and fetal weight in PE group were lower than those in the control group(P<0.05).1.2 Comparison of clinical indicators between the two groups of pregnant womenSerum total protein concentration in PE group and control group were(56.3 ± 6.8)g/L and(61.6 ± 5.5)g/L respectively,albumin levels were(29.8 ± 4.2)g/L and(34.7 ± 2.9)g/L respectively,urea levels were(4.0 ± 0.8)mmol/l and(3.5 ± 0.7)mmol/l respectively,uric acid levels were(317.4 ± 94.5)?mol/L and(263.0 ± 66.8)?mol/L respectively,creatinine concentration respectively for(53.6 ± 11.5)?mol/L and(44.6 ± 6.6)?mol/L,?2-microglobulin concentration respectively for(2.3 ± 0.6)mg/L and(1.8 ± 0.4)mg/L,?1-microglobulin concentration respectively for(27.5 ± 7.7)mg/L and(24.7 ± 4.1)mg/L,Cystatin c concentration respectively for(1.6 ± 0.4)?mol/L and(1.1 ± 0.2)?mol/l,and concentrations of lactate dehydrogenase were respectively(256.6 ± 61.8)U/L and(198.5 ± 30.1)U/L.After statistical analysis,the concentrations of urea?uric acid?creatinine??2-microglobulin??1-microglobulin?cystatin c and lactate dehydrogenase in PE serum were higher than those in the control group(P<0.05).The concentrations of total protein and albumin in PE group were lower than those in the control group(P<0.05).2 IFI16 protein localization and expressio in placenta tissuesIFI16 was mainly localized in the trophoblast cells and vascular endothelial cells of the placenta.Compared with the control group,IFI16 protein in PE placenta tissue was significantly higher(the positive rates of IFI16 in normal placenta tissues and PE placenta tissues were 43% and 78% respectively,P<0.05).3 IFI16 mRNA and protein expression in placenta tissuesIFI16 mRNA expression level in PE placentas was 1.65 ± 0.08,the control group was 0.72 ± 0.05,compared with the control group,IFI16 mRNA expression in PE placentas was significantly higher(P<0.01).The expression level of IFI16 protien in PE placentas was 1.58 ± 0.06,the control group was 0.56 ± 0.03,compared with the control group,IFI16 protein expression in PE placentas was significantly increased(P<0.01).4 The levels of IFI16 and ET-1 in serum of two groups pregnant womenSerum IFI16 level in PE group was(20.68±8.9)ng/mL,the control group was(10.08 ± 4.1)ng/mL.Compared with the control group,serum IFI16 level was significantly higher in PE group(P<0.01).The concentration of ET-1 in serum of PE pregnant women was(41.6 ± 9.3)ng/L,normal pregnant women was(11.0 ± 4.9)ng/L,compared with normal pregnant women,serum ET-1 concentration in PE group was significantly increased(P<0.01).5 The correlation between serum IFI16 levels and clinical indicatorsPearson correlation analysis showed that serum IFI16 levels in PE group was significantly correlated with systolic blood pressure(r=0.639,P<0.01),diastolic blood pressure(r=0.514,P<0.01),24-hour proteinuria(r=0.707,P<0.01),Cystatin c(r=0.347,P<0.05)and serum ET-1 levels(r=0.616,P<0.01),and negatively correlated with serum albumin(r=-0.366,P<0.05);Serum IFI16 levels in PE group have no obvious relevance with average age,gestational age at sampling,gestational age of delivery,urea,uric acid,creatinine,?2-microglobulin,?1-microglobulin,and lactate dehydrogenase.6 The values of serum IFI16 level in the prediction of preeclampsiaROC curve analysis demonstrated that a 13.89 ng/mL cutoff value for IFI16 serum concentrations identified women with PE with 77.78% sensitivity and 83.33% specificity(AUC=0.859).An IFI16 serum concentration cutoff value of 15.6 ng/mL discriminated between severe PE and mild PE with 90% sensitivity and 48% specificity(AUC=0.658).ConclusionIFI16 may be involved in PE pathogenesis through injury of vascular endothelial cells and is likely to become the new biological indicator for predicting PE.