Wnt/β-catenin信号通路对重度子痫前期患者胎盘滋养层细胞侵袭和增殖的影响
|
摘要
为了阐明Wnt/β-catenin信号通路在子痫前期发生发展中的作用机制,本研究应用RT-PCR检测了子痫前期和正常妊娠妇女胎盘中的Wnt1、β-catenin和cyclinD1的mRNA水平。通过Western blotting检测了Wnt1、β-catenin、Dickkopf-1 (DKK1)和糖原合成酶激酶3β(GSK-3β)蛋白的表达水平。使用免疫组化定位胎盘中Wnt1、β-catenin和DKK1蛋白的表达。研究显示,与对照组正常胎盘相比,重度子痫前期胎盘中Wnt1、β-catenin和cyclinD1的mRNA表达水平显著降低。Western blotting结果显示,对照组Wnt1、β-catenin和GSK-3β蛋白表达水平显著升高,而DKK1表达水平显著降低。此外,与对照组相比,子痫前期组胎盘中Wnt1和β-catenin的染色强度较弱,而DKK1的染色强度明显增强。说明子痫前期患者胎盘中Wnt/β-catenin信号通路及其下游靶基因被抑制,导致滋养层的侵袭和增殖能力降低,从而促进了子痫前期的发生发展。
To elucidate the mechanism of action of Wnt/β-catenin signaling pathway in the development of preeclampsia. In this study, RT-PCR was used to detect the mRNA levels of Wnt1, β-catenin and cyclinD1 in the placenta of preeclamptic and normal pregnant women. The expression levels of Wnt1, β-catenin, Dickkopf-1(DKK1) and glycogen synthase kinase 3β(GSK-3β) protein were detected by Western blotting. Immunohistochemistry was used to localize the expression of Wnt1, β-catenin and DKK1 proteins in the placenta. Studies showed that the mRNA expression levels of Wnt1, β-catenin and cyclinD1 in severe preeclamptic placenta were significantly lower than those in the control group. Western blotting results showed that the expression levels of Wnt1,β-catenin and GSK-3β protein in the control group were significantly increased, while the expression level of DKK1 was significantly decreased. In addition, compared with the control group, the staining intensity of Wnt1 and β-catenin in the placenta of the preeclampsia group was weak, but the staining intensity of DKK1 was significantly enhanced. It indicated that the Wnt/β-catenin signaling pathway and its downstream target genes are inhibited in the placenta of preeclampsia patients, resulting in decreased invasion and proliferation of trophoblasts,which promotes the development of preeclampsia.
To elucidate the mechanism of action of Wnt/β-catenin signaling pathway in the development of preeclampsia. In this study, RT-PCR was used to detect the mRNA levels of Wnt1, β-catenin and cyclinD1 in the placenta of preeclamptic and normal pregnant women. The expression levels of Wnt1, β-catenin, Dickkopf-1(DKK1) and glycogen synthase kinase 3β(GSK-3β) protein were detected by Western blotting. Immunohistochemistry was used to localize the expression of Wnt1, β-catenin and DKK1 proteins in the placenta. Studies showed that the mRNA expression levels of Wnt1, β-catenin and cyclinD1 in severe preeclamptic placenta were significantly lower than those in the control group. Western blotting results showed that the expression levels of Wnt1,β-catenin and GSK-3β protein in the control group were significantly increased, while the expression level of DKK1 was significantly decreased. In addition, compared with the control group, the staining intensity of Wnt1 and β-catenin in the placenta of the preeclampsia group was weak, but the staining intensity of DKK1 was significantly enhanced. It indicated that the Wnt/β-catenin signaling pathway and its downstream target genes are inhibited in the placenta of preeclampsia patients, resulting in decreased invasion and proliferation of trophoblasts,which promotes the development of preeclampsia.
引文
Herzog E.M.,Eggink A.J.,Reijnierse A.,Kerkhof M.A.,de Krijger R.R.,Roks A.J.,Reiss I.K.,Nigg A.L.,Eilers P.H.,Steegers E.A.,and Steegers-Theunissen R.P.,2017,Impact of early-and late-onset preeclampsia on features of placental and newborn vascular health,Placenta,49:72-79
Liao D.J.,Thakur A.,Wu J.,Biliran H.,and Sarkar F.H.,2007,Perspectives on c-Myc,Cyclin D1,and their interaction in cancer formation,progression,and response to chemotherapy,Crit.Rev.Oncog.,13(2):93-158
Ngwenya S.,2017,Severe preeclampsia and eclampsia:incidence,complications,and perinatal outcomes at a low-resource setting,Mpilo Central Hospital,Bulawayo,Zimbabwe,Int.J.Womens Health,9:353-357
Pollheimer J.,Loregger T.,Sonderegger S.,Saleh L.,Bauer S.,Bilban M.,Czerwenka K.,Husslein P.,and Knfler M.,2006,Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast,American Journal of Pathology,168(4):1134-1147
Rao H.,Bai Y.,Zhang F.,Li Q.,Zhuang B.,Luo X.,and Qi H.,2019,The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia,J.Matern.Fetal.Neonatal.Med.,32(12):2069-2078
Sonderegger S.,Husslein H.,Leisser C.,and Knfler M.,2007,Complex expression pattern of wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes,Placenta,28(supp-S):97-102
Valensise H.,Vasapollo B.,Gagliardi G.,and Novelli G.P.,2008,Early and late preeclampsia:two different maternal hemodynamic states in the latent phase of the disease,Hypertension,52(5):873-880
Zhang Z.,Li H.,Zhang L.,Jia L.,and Wang P.,2013,Differential expression of beta-catenin and dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies:a comparative study,Reproductive Biology&Endocrinology Rb&E,11(1):17
Zhang Z.,Wang X.,Zhang L.,Shi Y.,Wang J.,and Yan H.,2017,Wnt/β-catenin signaling pathway in trophoblasts and abnormal activation in preeclampsia(Review),Molecular Medicine Reports,16(2):1007-1013
Liao D.J.,Thakur A.,Wu J.,Biliran H.,and Sarkar F.H.,2007,Perspectives on c-Myc,Cyclin D1,and their interaction in cancer formation,progression,and response to chemotherapy,Crit.Rev.Oncog.,13(2):93-158
Ngwenya S.,2017,Severe preeclampsia and eclampsia:incidence,complications,and perinatal outcomes at a low-resource setting,Mpilo Central Hospital,Bulawayo,Zimbabwe,Int.J.Womens Health,9:353-357
Pollheimer J.,Loregger T.,Sonderegger S.,Saleh L.,Bauer S.,Bilban M.,Czerwenka K.,Husslein P.,and Knfler M.,2006,Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast,American Journal of Pathology,168(4):1134-1147
Rao H.,Bai Y.,Zhang F.,Li Q.,Zhuang B.,Luo X.,and Qi H.,2019,The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia,J.Matern.Fetal.Neonatal.Med.,32(12):2069-2078
Sonderegger S.,Husslein H.,Leisser C.,and Knfler M.,2007,Complex expression pattern of wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes,Placenta,28(supp-S):97-102
Valensise H.,Vasapollo B.,Gagliardi G.,and Novelli G.P.,2008,Early and late preeclampsia:two different maternal hemodynamic states in the latent phase of the disease,Hypertension,52(5):873-880
Zhang Z.,Li H.,Zhang L.,Jia L.,and Wang P.,2013,Differential expression of beta-catenin and dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies:a comparative study,Reproductive Biology&Endocrinology Rb&E,11(1):17
Zhang Z.,Wang X.,Zhang L.,Shi Y.,Wang J.,and Yan H.,2017,Wnt/β-catenin signaling pathway in trophoblasts and abnormal activation in preeclampsia(Review),Molecular Medicine Reports,16(2):1007-1013