Partitioning-defective protein 6 (Par6), a regulator of cell polarity, is emerging as a mediator of cell differentiation. Herein I sought to assess the contribution of Par6 to trophoblast fusion in normal and pathological human placentae. I hypothesized that Par6 regulates fusion in response to oxygen and transforming growth factor 3 (TGF3) and that this process is altered in preeclampsia (PE). Using silencing and overexpression strategies in choriocarcinoma BeWo cells, my results demonstrate Par6 negatively regulates trophoblast fusion via its roles on tight junctions and cytoskeleton dynamics. Additionally, Par6 expression is elevated in PE, a pathology characterized by placentalhypoxia, increased TGF3, and altered trophoblast fusion. Using low O2 conditions to model PE in BeWo and primary trophoblast cells, Par6 levels increased, and thisassociated with maintenance of tight junctions at cell boundaries and decreased fusion. Overall, my data provides insight into the mechanisms involving Par6 in contributing to the pathogenesis of PE.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/27361 |
| Date | 31 May 2011 |
| Creators | Sivasubramaniyam, Tharini |
| 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 |
Page generated in 0.002 seconds