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.
LeitnerYHarelSGevaREshelRYaffoAManyA. The neurocognitive outcome of IUGR children born to mothers with and without preeclampsia. J Matern Fetal Neonatal Med. 2012;25(11):2206–2208.
KumeT. Novel insights into the differential functions of Notch ligands in vascular formation. J Angiogenes Res. 2009;1:8.
6.
PanDRubinGM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell. 1997;90(2):271–280.
De StrooperBAnnaertWCupersP. A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature. 1999;398(6727):518–522.
9.
TaloraCCampeseAFBellaviaD. Notch signaling and diseases: an evolutionary journey from a simple beginning to complex outcomes. Biochim Biophys Acta. 2008;1782(9):489–497.
10.
AndersenPUosakiHShenjeLTKwonC. Non-canonical Notch signaling: emerging role and mechanism. Trends Cell Biol. 2012;22(5):257–265.
11.
HunkapillerNMGasperowiczMKapidzicM. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development. 2011;138(14):2987–2998.
12.
SahinZAcarNOzbeyOUstunelIDemirR. Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas. Acta Histochem. 2011;113(3):270–276.
13.
CobellisLMastrogiacomoAFedericoE. Distribution of Notch protein members in normal and preeclampsia-complicated placentas. Cell Tissue Res. 2007;330(3):527–534.
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.
ZhangWHAlexanderSBouvier-ColleMHMacfarlaneA. 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.
16.
KovoMSchreiberLBen-HaroushAGoldEGolanABarJ. The placental component in early-onset and late-onset preeclampsia in relation to fetal growth restriction. Prenat Diagn. 2012;32(7):632–637.
17.
HerrFSchreinerIBaalNPfarrerCZygmuntM. Expression patterns of Notch receptors and their ligands Jagged and Delta in human placenta. Placenta. 2011;32(8):554–563.
18.
LiuJFanHMaY. Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas. PLoS One. 2013;8(2):e56141.
19.
De FalcoMCobellisLGiraldiD. Expression and distribution of notch protein members in human placenta throughout pregnancy. Placenta. 2007;28(2-3):118–126.
20.
RinnociVNannucciSValentiR. Cerebral hemorrhages in CADASIL: report of four cases and a brief review. J Neurol Sci. 2013;330(1-2):45–51.
21.
RahmanMTNakayamaKRahmanM. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol. 2012;138(4):535–544.
22.
PancewiczJNicotC. Current views on the role of Notch signaling and the pathogenesis of human leukemia. BMC Cancer. 2011;11:502.
23.
YamaguchiNOyamaTItoE. NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2-negative human breast cancer cells. Cancer Res. 2008;68(6):1881–1888.
24.
OhashiSNatsuizakaMYashiro-OhtaniY. NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology. 2010;139(6):2113–2123.
25.
Sanchez-NinoMDOrtizA. Notch3 and kidney injury: never two without three. J Pathol. 2012;228(3):266–273.
26.
RaimondiLCiarapicaRDe SalvoM. 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.
CrockerI. Gabor Than award lecture 2006: pre-eclampsia and villous trophoblast turnover: perspectives and possibilities. Placenta. 2007;28 (suppl A):S4–S13.
29.
PrusacIKZekic TomasSRojeD. 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.
30.
VargasAToufailyCLeBellegoFRassartELafondJBarbeauB. Reduced expression of both syncytin 1 and syncytin 2 correlates with severity of preeclampsia. Reprod Sci. 2011;18(11):1085–1091.
31.
YangZYangCZhangSLiYChenJ. Notch2 inhibits proliferation of chronic myeloid leukemia cells. Oncol Lett. 2013;5(4):1390–1394.
32.
JinHGongWZhangCWangS. Epigallocatechin gallate inhibits the proliferation of colorectal cancer cells by regulating Notch signaling. Onco Targets Ther. 2013;6:145–153.
