Von Hippel Lindau (VHL) is a tumour suppressor protein classically known to target the α subunit of hypoxia inducible factor (HIF) for proteasomal degradation. Emerging evidence has underscored a novel role for VHL in both cell cycle regulation and extracellular matrix assembly. Herein, we provide evidence of VHL multitasking in normal and pathological placentation. Using ex vivo, first trimester human placental tissue and in vitro, JEG-3 choriocarcinoma cell line model we demonstrate that VHL plays a role in regulating the expression of cell cycle modulator CCND1 via a mechanism involving its inhibitor, p15 and HIF-2α. In addition, using a similar experimental strategy we provide evidence supporting a role for VHL in regulating the expression of fibronectin and its receptor integrin α5. Moreover, altered VHL expression observed in preeclampsia is associated with altered expression of cell cycle regulators and contributes to altered FN protein levels which are characteristic of this pathology.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/24558 |
| Date | 22 July 2010 |
| Creators | Deda, Livia |
| Contributors | Caniggia, Isabella |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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