title: Distribution of Notch protein members in normal and preeclampsia-complicated placentas.
abstract: Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry. In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21(Cip1) in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology.
authors.affiliation: Department of Gynaecology, Obstetric, and Reproductive Science, Second University of Naples, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cobellis
authors.forename: Annunziata
authors.initials: A
authors.lastname: Mastrogiacomo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Federico
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Schettino
authors.forename: Maria
authors.initials: M
authors.lastname: De Falco
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Manente
authors.forename: Gabriele
authors.initials: G
authors.lastname: Coppola
authors.forename: Marco
authors.initials: M
authors.lastname: Torella
authors.forename: Nicola
authors.initials: N
authors.lastname: Colacurci
authors.forename: Antonio
authors.initials: A
authors.lastname: De Luca
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000032:analysis* / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D002135:Calcium-Binding Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A