Interdisciplinary Graduate Programs Symposium
2011 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium
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Poster abstracts
Abstract:
Blood vessel formation is a tightly regulated process that serves a critical role in both health and disease. Initially, endothelial cells coalesce to form a nascent vessel, which then recruits mural cells that surround the tube to provide support and stability. It has become apparent that interactions between endothelial and mural cells are required for proper blood vessel formation. In a quest to investigate the mechanisms that govern this communication, we screened for molecules that were regulated by the interaction of endothelial cells and mural cells using a coculture model of angiogenesis. With this approach, we identified Syndecan-2 as one gene that is induced in mural cells by cocultured endothelial cells. Syndecan-2 is a heparan sulfate proteoglycan that serves as a receptor for extracellular matrix proteins and growth factors, and has been implicated in regulating angiogenesis. Investigations into the mechanism that governs endothelial-dependent induction of Syndecan-2, revealed a role for Notch signaling. Treatment with Notch signaling inhibitor DAPT and dominant-negative Mastermind blocked Syndecan-2 upregulation. In addition, silencing of Notch2 and Notch3 by siRNA prevented Syndecan-2 induction, and overexpression of the intracellular domain of either Notch2 or Notch3 drove the expression of Syndecan-2. Our lab previously showed induction of Notch3 by heterotypic cell interaction regulates vessel formation. The activation of Notch signaling is initiated by the binding of ligand to receptor, and this event is a potential target of Syndecan-2, as a transmembrane coreceptor. To test this hypothesis, we silenced Syndecan-2 and found the induction of Notch signaling was attenuated. These finding indicate Syndecan-2 and Notch signaling regulate each other reciprocally, and partially explain the mechanism of autoregulation of Notch3 in the context of heterotypic cell interaction.
References:
Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9: 653-660.
Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97: 512-523.
Lilly B, Kennard S (2009) Differential gene expression in a coculture model of angiogenesis reveals modulation of select pathways and a role for Notch signaling. Physiol Genomics 36: 69-78.
Chen E, Hermanson S, Ekker SC (2004) Syndecan-2 is essential for angiogenic sprouting during zebrafish development. Blood 103: 1710-1719.
Liu H, Kennard S, Lilly B (2009) NOTCH3 expression is induced in mural cells through an autoregulatory loop that requires endothelial-expressed JAGGED1. Circ Res 104: 466-475.
Xian X, Gopal S, Couchman JR (2009) Syndecans as receptors and organizers of the extracellular matrix. Cell Tissue Res.
Keywords: Angiogenesis, Syndecan-2, Notch
