Distribution of Notch protein members in normal and preeclampsia-complicated placentas.
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.
Cobellis
Luigi
L
Department of Gynaecology, Obstetric, and Reproductive Science, Second University of Naples, Naples, Italy.
Mastrogiacomo
Annunziata
A
Federico
Elisabetta
E
Schettino
Maria Teresa
MT
De Falco
Maria
M
Manente
Lucrezia
L
Coppola
Gabriele
G
Torella
Marco
M
Colacurci
Nicola
N
De Luca
Antonio
A
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
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