Preeclampsia is a pregnancy related disorder, characterized by proteinuria and hypertension. The pathogenesis of preeclampsia is poorly understood; however, two proteins, called sFlt-1 and sEng, were found to be highly elevated in the maternal plasma weeks prior to the onset of clinical symptoms. sFlt-1 and sEng are thought to inhibit VEGF and TGF-β receptor signalling respectively. In order to elucidate how these proteins may contribute to preeclampsia, we looked at their ability to affect the secretion of endothelin-1 (ET-1), a powerful vasoconstrictor, shown to be dysregulated in preeclampsia. We found that both TGF-β1 and BMP9, a recently described ligand for sEng, induce ET-1 secretion through Smad1/5/8 and p38 pathways. Moreover, we report that sEng and VEGF can efficiently block ET-1 secretion, induced by BMP9. We propose that the balance between VEGF and BMP9 signalling is disturbed during preeclampsia, leading to excessive release of ET-1, which in turn may cause hypertension.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42943 |
| Date | 28 November 2013 |
| Creators | Sotov, Valentin |
| Contributors | Letarte, Michelle |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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