Notch信号通路配体Jagged1与DLL4在子痫前期孕妇胎盘组织中的表达及意义
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摘要
目的探讨Notch信号通路配体Jagged1与DLL4在子痫前期孕妇胎盘组织中的表达及意义。方法选择接受剖宫产术分娩的子痫前期孕妇73例,根据病情,分为中轻度子痫前期孕妇37例(轻度组)和重度子痫前期孕妇36例(重度组)。另选取同期正常妊娠且接受剖宫产术分娩的孕妇35例作为对照组。采用免疫组化SP法定位胎盘组织中Jagged1与DLL4的表达,采用Western blot法检测Jagged1与DLL4蛋白表达水平。结果在对照组、轻度组、重度组孕妇胎盘组织中,Jagged1主要表达于绒毛滋养层细胞和血管内皮细胞,DLL4则主要表达于血管内皮细胞。对照组孕妇胎盘组织中Jagged1、DLL4蛋白表达水平均高于轻度组和重度组,轻度组孕妇胎盘组织中Jagged1、DLL4蛋白表达水平均高于重度组,差异均有统计学意义(均P<0.05)。结论子痫前期患者胎盘组织中Notch信号通路配体Jagged1与DLL4表达失衡,与子痫前期的发生、发展有密切联系,两者联合检测有望为子痫前期的防治提供新的靶点。
Objective To investigate the expression of Notch signal channel ligand Jagged1 and DLL4 in placental tissue of patients with preeclampsia. Methods Seventy three patients with preeclampsia, including 37 mild cases(mild group) and 36 severe cases(severe growp) were enrolled in the study, and 35 cases of normal pregnant women were selected as control group.The expression of Jagged1 and DLL4 in placenta was detected by immunohistochemical SP method and Western blot. Results In the control group, mild group and severe group, Jagged1 was mainly expressed in villous trophoblast cells and vascular endothelial cells, while DLL4 was mainly expressed in vascular endothelial cells. The levels of Jagged1 protein and DLL4 protein in the placenta tissue of the control group were higher than those in the mild group and the severe group(all P<0.05), while in the mild group, the levels of Jagged1 protein and DLL4 protein in the placenta tissues were higher than those in the severe group(both P<0.05). Conclusion The expression of Notch signal channel ligand Jagged1 and DLL4 in the placental tissue of preeclampsia patients is unbalanced, which is closely related to the occurrence and development of preeclampsia. Jagged1 and DLL4 in the placenta may be a new target for the prevention and treatment of preeclampsia.
Objective To investigate the expression of Notch signal channel ligand Jagged1 and DLL4 in placental tissue of patients with preeclampsia. Methods Seventy three patients with preeclampsia, including 37 mild cases(mild group) and 36 severe cases(severe growp) were enrolled in the study, and 35 cases of normal pregnant women were selected as control group.The expression of Jagged1 and DLL4 in placenta was detected by immunohistochemical SP method and Western blot. Results In the control group, mild group and severe group, Jagged1 was mainly expressed in villous trophoblast cells and vascular endothelial cells, while DLL4 was mainly expressed in vascular endothelial cells. The levels of Jagged1 protein and DLL4 protein in the placenta tissue of the control group were higher than those in the mild group and the severe group(all P<0.05), while in the mild group, the levels of Jagged1 protein and DLL4 protein in the placenta tissues were higher than those in the severe group(both P<0.05). Conclusion The expression of Notch signal channel ligand Jagged1 and DLL4 in the placental tissue of preeclampsia patients is unbalanced, which is closely related to the occurrence and development of preeclampsia. Jagged1 and DLL4 in the placenta may be a new target for the prevention and treatment of preeclampsia.
引文
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[12]Spinner NB,Colliton RP,Crosnier C,et al.Jagged1 mutations in alagille syndrome[J].Human Mutation,2015,17(1):18-33.DOI:10.1002/1098-1004(2001)17:1%3C18::AID-HUMU3%3E3.0.CO;2-T.
[13]Colliton RP,Bason L,Lu F,et al.Mutation analysis of Jagged1(JAG1)in Alagille syndrome patients[J].Human Mutation,2015,17(2):151-152.DOI:10.1002/1098-1004(200102)17:2%3C151::AID-HUMU8%3E3.0.CO;2-T.
[14]Otti GR,Saleh L,Velicky P,et al.Notch2 controls prolactin and insulin-like growth factor binding protein-1 expression in decidualizing human stromal cells of early pregnancy[J].PLo S One,2014,9(11):e112723.DOI:10.1371/journal.pone.0112723.
[2]Polat I,Gedikbasi A,Kiyak H,et al.Double notches:association of uterine artery notch forms with pregnancy outcome and severity of preeclampsia[J].Hypertension in Pregnancy,2015,34(1):90.DOI:10.3109/10641955.2014.982330.
[3]Nanjo S,Matsushita A,Yahata T,et al.Expression of Notch signaling in placental tissues with preeclampsia(PE)and/or fetal growth restriction(FGR)[J].Placenta,2016,46(2):107-108.DOI:10.1016/j.placenta.2016.08.022.
[4]中华医学会妇产科学分会妊娠期高血压疾病学组.妊娠期高血压疾病诊治指南(2012版)[J].中华妇产科杂志,2012,47(6):476-480.DOI:10.3760/cma.j.issn.0529-567x.2012.06.018.
[5]中华医学会妇产科学分会妊娠期高血压疾病学组.妊娠期高血压疾病诊治指南(2015)[J].中华妇产科杂志,2015,50(10):721-728.DOI:10.3760/cma.j.issn.1007-9408.2016.03.001.
[6]Fragkiadaki P,Soulitzis N,Sifakis S,et al.Downregulation of Notch Signaling Pathway in Late Preterm and Term Placentas from Pregnancies Complicated by Preeclampsia[J].PLo S One,2015,10(5):e0126163.DOI:10.1371/journal.pone.0126163.
[7]Shimanuki Y,Mitomi H,Fukumura Y,et al.Alteration of Delta-like ligand 1 and Notch 1 receptor in various placental disorders with special reference to early onset preeclampsia[J].Human Pathology,2015,46(8):1129-1137.DOI:10.1016/j.humpath.2015.03.013.
[8]Levin HI,Sullivanpyke CS,Papaioannou VE,et al.Dynamic maternal and fetal Notch activity and expression in placentation[J].Placenta,2017,55(2):5.DOI:10.1016/j.placenta.2017.04.014.
[9]Uyar I,Kurt S,Demirtas O,et al.The value of uterine artery Doppler and NT-pro BNP levels in the second trimester to predict preeclampsia[J].Archives of Gynecology&Obstetrics,2015,291(6):1-6.DOI:10.1007/s00404-014-3563-3.
[10]Santa LM,Teshima LY,Forero JV,et al.AngiomiRs:Potential Biomarkers of Pregnancy's Vascular Pathologies[J].Journal of Pregnancy,2015,2015:320386.DOI:10.1155/2015/320386.
[11]Grochowski CM,Loomes KM,Spinner NB.Jagged1(JAG1):Structure,Expression,and Disease Associations[J].Gene,2016,576(1):381-384.DOI:10.1016/j.gene.2015.10.065.
[12]Spinner NB,Colliton RP,Crosnier C,et al.Jagged1 mutations in alagille syndrome[J].Human Mutation,2015,17(1):18-33.DOI:10.1002/1098-1004(2001)17:1%3C18::AID-HUMU3%3E3.0.CO;2-T.
[13]Colliton RP,Bason L,Lu F,et al.Mutation analysis of Jagged1(JAG1)in Alagille syndrome patients[J].Human Mutation,2015,17(2):151-152.DOI:10.1002/1098-1004(200102)17:2%3C151::AID-HUMU8%3E3.0.CO;2-T.
[14]Otti GR,Saleh L,Velicky P,et al.Notch2 controls prolactin and insulin-like growth factor binding protein-1 expression in decidualizing human stromal cells of early pregnancy[J].PLo S One,2014,9(11):e112723.DOI:10.1371/journal.pone.0112723.