Wnt/β-catenin signaling pathway in severe preeclampsia

  • Xiaofang Wang
  • Zhan Zhang
  • Xianxu Zeng
  • Jinming Wang
  • Linlin Zhang
  • Wanyu Song
  • Ying Shi
Original Paper

Abstract

This study aims to elucidate the mechanisms of Wnt/β-catenin signaling pathway in the development of preeclampsia (PE). The mRNA levels of Wnt1, β-catenin, c-myc and cyclinD1 were determined by real-time PCR in the placentas. Moreover, the expression levels of Wnt1, β-catenin, Dickkopf-1 (DKK1) and glycogen synthase kinase 3β (GSK-3β) proteins were detected by Western blot. Immunohistochemistry was used in placental tissue microarray to localize the expression of Wnt1, β-catenin, DKK1 proteins in the placentas of two groups. Compared with the control placentas, the mRNA levels of Wnt1, β-catenin, c-myc and cyclinD1 were decreased in the severe preeclamptic placentas. The Western blot results showed that the expression levels of Wnt1, β-catenin, and GSK-3β proteins were significantly elevated in the control group, while the expression level of DKK1 was significantly decreased. In addition, the staining intensity of Wnt1, β-catenin were weaker in the placentas of the severe PE group while the staining intensity of DKK1 was significantly stronger in the placentas of the severe PE group. Wnt/β-catenin signaling pathway may play a significant role in the pathogenesis of PE by regulating the invasion and proliferation of trophoblast.

Keywords

Wnt1 β-Catenin Preeclampsia Trophoblast Placenta 

Notes

Acknowledgements

The present study was supported by the National Natural Science Foundation (Grant Number 81501285).

Compliance with ethical standards

Conflict of interest

None of the authors has any conflict of interest.

References

  1. Ananth CV, Keyes KM, Wapner RJ (2013) Pre-eclampsia rates in the United States, 1980–2010: age-period-cohort analysis. BMJ 347:1–9.  https://doi.org/10.1136/bmj.f6564 CrossRefGoogle Scholar
  2. Committee on Obstetric Practice A (2002) Practice bulletin #33: diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol 99(2):347–365Google Scholar
  3. Goldman-Wohl D, Yagel S (2002) Regulation of trophoblast invasion: from normal implantation to pre-eclampsia. Mol Cell Endocrinol 187:233–238.  https://doi.org/10.1016/S0303-7207(01)00687-6 CrossRefPubMedGoogle Scholar
  4. Herzog EM, Eggink AJ, Reijnierse A et al (2017) Impact of early- and late-onset preeclampsia on features of placental and newborn vascular health. Placenta 49:72–79.  https://doi.org/10.1016/j.placenta.2016.11.014 CrossRefPubMedGoogle Scholar
  5. Hubel CA, Wallukat G, Wolf M et al (2007) Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension 49:612–617CrossRefGoogle Scholar
  6. Kaufmann P, Black S, Huppertz B (2003) Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 69:1–7.  https://doi.org/10.1095/biolreprod.102.014977 CrossRefPubMedGoogle Scholar
  7. Kestler HA, Kuhl M (2008) From individual Wnt pathways towards a Wnt signalling network. Philos Trans R Soc B Biol Sci 363:1333–1347.  https://doi.org/10.1098/rstb.2007.2251 CrossRefGoogle Scholar
  8. Kumar P, Luo Y, Tudela C et al (2013) The c-Myc-regulated microRNA-17 92 (miR-17 92) and miR-106a 363 clusters target hCYP19A1 and hGCM1 to inhibit human trophoblast differentiation. Mol Cell Biol 33:1782–1796.  https://doi.org/10.1128/MCB.01228-12 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Liao DJ, Thakur A, Wu J et al (2007) Perspectives on c-Myc, cyclin D1, and their interaction in cancer formation, progression, and response to chemotherapy. Crit Rev Oncog 13:93–158.  https://doi.org/10.1615/CritRevOncog.v13.i2.10 CrossRefPubMedGoogle Scholar
  10. MacDonald BT, Tamai K, He X (2010) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Biol 17:9–26.  https://doi.org/10.1016/j.devcel.2009.06.016.Google Scholar
  11. Mol BWJ, Roberts CT, Thangaratinam S et al (2016) Pre-eclampsia. Lancet 387:999–1011.  https://doi.org/10.1016/S0140-6736(15)00070-7 CrossRefPubMedGoogle Scholar
  12. Pollheimer J, Loregger T, Sonderegger S et al (2006) Activation of the canonical wingless/T-cell factor signaling pathway promotes invasive differentiation of human trophoblast. Am J Pathol 168:1134–1147.  https://doi.org/10.2353/ajpath.2006.050686 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Rao H, Bai Y, Zhang F et al (2018) The role of SATB1 in HTR8/SVneo cells and pathological mechanism of preeclampsia. J Matern Fetal Neonatal Med 16:1–10.  https://doi.org/10.1080/14767058.2018.1425387 CrossRefGoogle Scholar
  14. Redman CWG, Sacks GP, Sargent IL (1999) Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 180:499–506.  https://doi.org/10.1016/S0002-9378(99)70239-5 CrossRefPubMedGoogle Scholar
  15. Redman CW, Sargent IL, Staff AC (2014) IFPA senior award lecture: making sense of pre-eclampsia—two placental causes of preeclampsia? Placenta 35:S20–S25.  https://doi.org/10.1016/j.placenta.2013.12.008 CrossRefPubMedGoogle Scholar
  16. Romero R, Chaiworapongsa T (2013) Preeclampsia: a link between trophoblast dysregulation and an antiangiogenic state. J Clin Invest 123:2775–2777.  https://doi.org/10.1172/JCI70431 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Sabai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. Lancet 365:785–799.  https://doi.org/10.1016/S0140-6736(05)17987-2 CrossRefGoogle Scholar
  18. Sonderegger S, Husslein H, Leisser C, Knöfler M (2007) Complex expression pattern of Wnt ligands and frizzled receptors in human placenta and its trophoblast subtypes. Placenta 28:1–12.  https://doi.org/10.1016/j.placenta.2006.11.003 CrossRefGoogle Scholar
  19. Tranquilli AL, Landi B, Giannubilo SR, Sibai BM (2012) Preeclampsia: no longer solely a pregnancy disease. Pregnancy Hypertens 2:350–357.  https://doi.org/10.1016/j.preghy.2012.05.006 CrossRefPubMedGoogle Scholar
  20. Tulac S, Nayak NR, Kao LC et al (2003) Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. J Clin Endocrinol Metab 88:3860–3866.  https://doi.org/10.1210/jc.2003-030494 CrossRefPubMedGoogle Scholar
  21. Valensise H, Vasapollo B, Gagliardi G, Novelli GP (2008) Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension 52:873–880.  https://doi.org/10.1161/HYPERTENSIONAHA.108.117358 CrossRefPubMedGoogle Scholar
  22. Valenta T, Hausmann G, Basler K (2012) The many faces and functions of Î 2-catenin. EMBO J 31:2714–2736.  https://doi.org/10.1038/emboj.2012.150 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Von Dadelszen P, Magee LA, Roberts JM (2003) Subclassification of preeclampsia. Hypertens Pregnancy 22:143–148.  https://doi.org/10.1081/PRG-120021060 CrossRefGoogle Scholar
  24. Zhang Z, Li H, Zhang L et al (2013a) Differential expression of beta-catenin and dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies: a comparative study. Reprod Biol Endocrinol 4:17.  https://doi.org/10.1186/1477-7827-11-17 CrossRefGoogle Scholar
  25. Zhang Z, Zhang L, Zhang L et al (2013b) Association of Wnt2 and sFRP4 expression in the third trimester placenta in women with severe preeclampsia. Reprod Sci 20:981–989.  https://doi.org/10.1177/1933719112472740 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Zhang Z, Wang X, Zhang L et al (2017) Wnt/β-catenin signaling pathway in trophoblasts and abnormal activation in preeclampsia (Review). Mol Med Rep 16:1007–1013.  https://doi.org/10.3892/mmr.2017.6718 CrossRefPubMedGoogle Scholar
  27. Zhang Z, Wang X, Wang J, Zhang L (2018) The decreased expression of Stat3 and p-Stat3 in preeclampsia-like rat placenta. J Mol Histol 49:175–183.  https://doi.org/10.1007/s10735-018-9757-4 CrossRefPubMedGoogle Scholar
  28. Zhu L, Zhang Z, Zhang L et al (2015) HMGB1-RAGE signaling pathway in severe preeclampsia. Placenta 36:1148–1152.  https://doi.org/10.1016/j.placenta.2015.08.006 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical LaboratoryThe Third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Department of Obstetrics and GynecologyThe Third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  3. 3.Department of PathologyThe Third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Department of Obstetrics and GynecologyThe People’s Hospital of Henan ProvinceZhengzhouChina
  5. 5.The Third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Personalised recommendations