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Expression of Notch Family Proteins in Placentas From Patients With Early-Onset Severe Preeclampsia

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Abstract

Objectives

This study is aimed to identify the expression of Notch family proteins in placentas from patients with early-onset severe preeclampsia.

Study Design

The expression of Notch family proteins in placentas was investigated by immunohistochemistry, Western blotting, and real-time reverse transcription–polymerase chain reaction (RT-PCR).

Results

The profile of distribution of all Notch family proteins in placentas from patients with early-onset severe preeclampsia is similar to that in normal placentas. All Notch family proteins are expressed in placental trophoblasts. Moreover, Notch1 and Jagged1 (Jag1) are detected in placental endothelial cells. Real-time RT-PCR showed that messenger RNA levels of Notch2 and Delta-like4 (Dll4) in placentas from patients with early-onset severe preeclampsia are lower than that of normal placentas. Western blotting showed a significant increase in Notch3 expression and a significant decrease in Notch2 expression in placentas from patients with early-onset severe preeclampsia relative to those in normal placentas.

Conclusion

The results suggest that Notch2 and Notch3 may play some roles in the pathogenesis of preeclampsia.

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References

  1. Leitner Y, Harel S, Geva R, Eshel R, Yaffo A, Many A. The neurocognitive outcome of IUGR children born to mothers with and without preeclampsia. J Matern Fetal Neonatal Med. 2012; 25(11):2206–2208.

    Article  CAS  Google Scholar 

  2. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Preeclampsia. Lancet. 2010; 376(9741):631–644.

    Article  Google Scholar 

  3. Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006;7(9):678–689.

    Article  CAS  Google Scholar 

  4. Fortini ME, Bilder D. Endocytic regulation of Notch signaling. Curr Opin Genet Dev. 2009;19(4):323–328.

    Article  CAS  Google Scholar 

  5. Kume T. Novel insights into the differential functions of Notch ligands in vascular formation. J Angiogenes Res. 2009;1:8.

    Article  Google Scholar 

  6. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell. 1997;90(2):271–280.

    Article  CAS  Google Scholar 

  7. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature. 1998; 393(6683):382–386.

    Article  CAS  Google Scholar 

  8. De Strooper B, Annaert W, Cupers P, et al. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999;398(6727):518–522.

    Article  Google Scholar 

  9. Talora C, Campese AF, Bellavia D, et al. Notch signaling and diseases: an evolutionary journey from a simple beginning to complex outcomes. Biochim Biophys Acta. 2008;1782(9):489–497.

    Article  CAS  Google Scholar 

  10. Andersen P, Uosaki H, Shenje LT, Kwon C. Non-canonical Notch signaling: emerging role and mechanism. Trends Cell Biol. 2012; 22(5):257–265.

    Article  CAS  Google Scholar 

  11. Hunkapiller NM, Gasperowicz M, Kapidzic M, et al. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development. 2011;138(14): 2987–2998.

    Article  CAS  Google Scholar 

  12. Sahin Z, Acar N, Ozbey O, Ustunel I, Demir R. Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas. Acta Histochem. 2011;113(3):270–276.

    Article  CAS  Google Scholar 

  13. Cobellis L, Mastrogiacomo A, Federico E, et al. Distribution of Notch protein members in normal and preeclampsia-complicated placentas. Cell Tissue Res. 2007;330(3):527–534.

    Article  CAS  Google Scholar 

  14. National high blood pressure education program working group report on high blood pressure in pregnancy. Am J Obstet Gynecol. 1990;163(5 pt 1):1691–1712.

  15. Zhang WH, Alexander S, Bouvier-Colle MH, Macfarlane A. Incidence of severe pre-eclampsia, postpartum haemorrhage and sepsis as a surrogate marker for severe maternal morbidity in a European population-based study: the MOMS-B survey. BJOG. 2005;112(1):89–96.

    Article  Google Scholar 

  16. Kovo M, Schreiber L, Ben-Haroush A, Gold E, Golan A, Bar J. The placental component in early-onset and late-onset preeclampsia in relation to fetal growth restriction. Prenat Diagn. 2012; 32(7):632–637.

    Article  Google Scholar 

  17. Herr F, Schreiner I, Baal N, Pfarrer C, Zygmunt M. Expression patterns of Notch receptors and their ligands Jagged and Delta in human placenta. Placenta. 2011;32(8):554–563.

    Article  CAS  Google Scholar 

  18. Liu J, Fan H, Ma Y, et al. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas. PLoS One. 2013;8(2):e56141.

    Article  CAS  Google Scholar 

  19. De Falco M, Cobellis L, Giraldi D, et al. Expression and distribution of notch protein members in human placenta throughout pregnancy. Placenta. 2007;28(2–3):118–126.

    Article  Google Scholar 

  20. Rinnoci V, Nannucci S, Valenti R, et al. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330(1–2):45–51.

    Article  Google Scholar 

  21. Rahman MT, Nakayama K, Rahman M, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol. 2012;138(4):535–544.

    Article  CAS  Google Scholar 

  22. Pancewicz J, Nicot C. Current views on the role of Notch signaling and the pathogenesis of human leukemia. BMC Cancer. 2011;11: 502.

    Article  CAS  Google Scholar 

  23. Yamaguchi N, Oyama T, Ito E, et al. NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells. Cancer Res. 2008;68(6):1881–1888.

    Article  CAS  Google Scholar 

  24. Ohashi S, Natsuizaka M, Yashiro-Ohtani Y, et al. NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology. 2010;139(6):2113–2123.

    Article  CAS  Google Scholar 

  25. Sanchez-Nino MD, Ortiz A. Notch3 and kidney injury: never two without three. J Pathol. 2012;228(3):266–273.

    Article  CAS  Google Scholar 

  26. Raimondi L, Ciarapica R, De Salvo M, et al. Inhibition of Notch3 signalling induces rhabdomyosarcoma cell differentiation promoting p38 phosphorylation and p21(Cip1) expression and hampers tumour cell growth in vitro and in vivo. Cell Death Differ. 2012;19(5):871–881.

    Article  CAS  Google Scholar 

  27. Serafin V, Persano L, Moserle L, et al. Notch3 signalling promotes tumour growth in colorectal cancer. J Pathol. 2011;224(4):448–460.

    Article  CAS  Google Scholar 

  28. Crocker I. Gabor Than award lecture 2006: pre-eclampsia and villous trophoblast turnover: perspectives and possibilities. Placenta. 2007;28 (suppl A):S4–S13.

    Article  Google Scholar 

  29. Prusac IK, Zekic Tomas S, Roje D. Apoptosis, proliferation and Fas ligand expression in placental trophoblast from pregnancies complicated by HELLP syndrome or pre-eclampsia. Acta Obstet Gynecol Scand. 2011;90(10):1157–1163.

    Article  CAS  Google Scholar 

  30. Vargas A, Toufaily C, LeBellego F, Rassart E, Lafond J, Barbeau B. Reduced expression of both syncytin 1 and syncytin 2 correlates with severity of preeclampsia. Reprod Sci. 2011;18(11): 1085–1091.

    Article  CAS  Google Scholar 

  31. Yang Z, Yang C, Zhang S, Li Y, Chen J. Notch2 inhibits proliferation of chronic myeloid leukemia cells. Oncol Lett. 2013; 5(4):1390–1394.

    Article  CAS  Google Scholar 

  32. Jin H, Gong W, Zhang C, Wang S. Epigallocatechin gallate inhibits the proliferation of colorectal cancer cells by regulating Notch signaling. Onco Targets Ther. 2013;6:145–153.

    Article  CAS  Google Scholar 

  33. Dill MT, Tornillo L, Fritzius T, et al. Constitutive Notch2 signaling induces hepatic tumors in mice. Hepatology. 2013;57(4): 1607–1619.

    Article  CAS  Google Scholar 

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Correspondence to Jian-Hua Lin PhD.

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Zhao, WX., Huang, TT., Jiang, M. et al. Expression of Notch Family Proteins in Placentas From Patients With Early-Onset Severe Preeclampsia. Reprod. Sci. 21, 716–723 (2014). https://doi.org/10.1177/1933719113512530

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  • DOI: https://doi.org/10.1177/1933719113512530

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