Date of Award
Dr. Peeyush K. Lala
Dr. Alison Allan
Dr. Lynne-Marie Postovit
The human placenta is a highly invasive tumour-like organ in which fetal-derived trophoblast cells constitute the major cell type. A subpopulation of trophoblast cells, known as extravillous trophoblast, invades the uterine decidua and maternal arteries to establish sufficient fetal-maternal exchange to maintain healthy utero-placental homeostasis. Trophoblast invasion is highly regulated by a variety of factors at the fetal-maternal interface. Decorin is a member of the small leucine-rich proteoglycan family, produced by the decidua, and is a negative regulator of trophoblast invasiveness. I hypothesized that decorin inhibits vascular endothelial growth factor (VEGF)-stimulated endovascular differentiation and migration by interfering with signalling pathways downstream of VEGF Receptor (VEGFR)-2. Using in vitro migration and endothelial-like tube formation assays, I determined that decorin inhibits trophoblast migration and endovascular differentiation by interfering with VEGF-induced p38 and p44/p42 mitogen-activated protein kinase (MAPK) activation. These results have implications for the pathobiology of preeclampsia, a hypo-invasive trophoblast disorder in pregnancy.
Lala, Neena, "MECHANISMS OF DECORIN INHIBITION OF VEGF-STIMULATED HUMAN TROPHOBLAST MIGRATION AND ACQUISITION OF AN ENDOVASCULAR PHENOTYPE" (2010). Digitized Theses. 4069.