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Modulation of Endothelial Cell Responses by Different TGFβ Isoforms and Oxygen Levels and Their Potential Impact on Angiogenesis

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dc.contributor.advisor Viloria-Petit, Alicia Doerr, Meghan 2015-01-07T20:38:28Z 2015-01-07T20:38:28Z 2014-12 2014-12-08 2015-01-07
dc.description.abstract Angiogenesis is vital for both normal tissue homeostasis and tumor progression via tumor angiogenesis. This process is regulated by many factors including VEGF, TGFβ and oxygen levels. All of these factors are present in the tumor microenviroment, suggesting they might interact to govern tumor angiogenesis. Endothelial to Mesenchymal Transition (EnMT) may also play a role in angiogenesis because some of the same factors also regulate this process. In this study, it was first confirmed that TGFβ treatment with either isoform 1 or 2 at a 5 ng/mL dose preferentially activates SMAD2 and not SMAD1, the effector proteins of the TGFβ pathway, under normal or low oxygen conditions. This suggests that high doses of either isoform favor the TGFβRII/ALK5 pathway. Next it was determined how activation of this pathway affected protein levels of endothelial cell and EnMT markers. It was found that TGFβ treatment increased the levels of a key EnMT-associated transcription factor, Snail, and decreased the levels of the adhesion protein, VE-cadherin. This response was consistent with an EnMT response. Lastly, it was determined how changes in these factors affected the angiogenic response of the bovine aortic endothelial cell line under study. It was found that treatment with either isoform of TGFβ in both oxygen conditions inhibited endothelial cell migration and cord formation, suggesting that TGFβ induced EnMT-like changes might not necessarily reflect the migratory and invasive components of an angiogenic response. More studies are necessary to establish the role of Snail in angiogenic response to TGFβ. en_US
dc.description.sponsorship Natural Sciences and Engineering Research Council of Canada; Ontario Veterinary College Fellowship en_US
dc.language.iso en en_US
dc.publisher University of Guelph en_US
dc.rights Attribution-NonCommercial-NoDerivs 2.5 Canada *
dc.rights.uri *
dc.subject Angiogenesis en_US
dc.subject Endothelial to Mesenchymal Transition en_US
dc.subject TGFβ en_US
dc.subject Hypoxia en_US
dc.title Modulation of Endothelial Cell Responses by Different TGFβ Isoforms and Oxygen Levels and Their Potential Impact on Angiogenesis en_US
dc.type Thesis en_US Biomedical Sciences en_US Master of Science en_US Department of Biomedical Sciences en_US University of Guelph en_US

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Attribution-NonCommercial-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 2.5 Canada
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