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Investigating the dose-dependent signalling of Transforming Growth Factor-Beta in bovine aortic endothelial cells

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Title: Investigating the dose-dependent signalling of Transforming Growth Factor-Beta in bovine aortic endothelial cells
Author: Richard, Amy
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Viloria-Petit, Alicia
Abstract: Transforming growth factor-beta (TGFβ) is an important signaling molecule that regulates several cellular processes including angiogenesis. However, its effects on angiogenesis are complex, with it being pro-angiogenic only at low concentrations (Pepper et al., 1993). Evidence suggests that downstream signaling pathways of TGFβ may be activated in a dose-dependent fashion. In fact, previous work in our laboratory has shown that the non-canonical Par6 polarity pathway gets preferentially activated at low concentrations. Considering the different cellular effects of downstream signaling pathways, we propose that TGFβ may modulate its effects on angiogenesis via differential activation of the canonical Smad and non-canonical Akt, FAK, NFκB and Par6 polarity signaling pathways. Based on this premise, bovine aortic endothelial cells were treated with TGFβ1 and TGFβ2 at concentrations ranging from 0.05 to 5 ng/mL. The activation patterns of canonical and non-canonical signaling pathways were studied via western blotting; with the use of phospho-specific antibodies against Smad2, Akt, FAK and NFκB. Preliminary results reveal that high concentrations of both TGFβ1 and TGFβ2 (5 ng/mL) cause preferential activation of Smad2, while the Akt, FAK and NFκB signaling pathways do not appear to become activated in response to TGFβ1 or TGFβ2 at the concentrations and time points studied. These results suggest the effect of TGFβ on angiogenesis may not involve Akt, FAK or NFκB signaling, but may involve dose-dependent signaling of the Smad signaling pathway.
Date: 2012-09
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