Role of Transforming Growth Factor Beta in Angiogenesis
Transforming growth factor beta (TGFβ) is a pleiotropic factor that plays pivotal roles in both vasculogenesis and angiogenesis and thus is indispensable for development and homeostasis of the vascular system. TGFβ drives vascular responses via its bindin
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Role of Transforming Growth Factor Beta in Angiogenesis Alicia Viloria-Petit, Amy Richard, Sonja Zours, Mai Jarad, and Brenda L. Coomber
Abstract Transforming growth factor beta (TGFβ) is a pleiotropic factor that plays pivotal roles in both vasculogenesis and angiogenesis and thus is indispensable for development and homeostasis of the vascular system. TGFβ drives vascular responses via its binding to a TGFβ receptor complex formed by type I and type II receptors, as well as type III co-receptors present on both endothelial and mural cells. Signaling by these receptors is context-dependent and tightly regulated, particularly on cultured endothelial cells, where TGFβ can either promote or suppress endothelial migration, proliferation, permeability, and sprouting. These, together with evidence obtained from knockout animals for different TGFβ receptor types, and genetic studies in humans linking mutations in TGFβ signaling components to cardiovascular syndromes, suggest that TGFβ is a central mediator of angiogenesis, where it may play contrasting roles depending on the stage of the process. This review presents an overview of knowledge accumulated to date on TGFβ’s role in angiogenesis as well as vascular biology and vascular disease and discusses potential applications of this knowledge to the treatment of angiogenesis-dependent diseases such as cancer. Keywords TGFβ • ALK • Endoglin • Smad • Endothelial cell • Pericyte • Angiogenesis • HHT • Fibrosis • Cancer
A. Viloria-Petit (*) • A. Richard • S. Zours • M. Jarad • B.L. Coomber () Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1 e-mail: [email protected]; [email protected]
J.L. Mehta and N.S. Dhalla (eds.), Biochemical Basis and Therapeutic Implications of Angiogenesis, Advances in Biochemistry in Health and Disease 6, DOI 10.1007/978-1-4614-5857-9_2, © Springer Science+Business Media New York 2013
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TGFb Molecule Family: Sources, Activation, and Regulation of Transcription The TGFb Family
The transforming growth factor beta (TGFβ) superfamily consists of 33 members, most of which are dimeric, secreted polypeptides that regulate proliferation, survival/apoptosis, migration, adhesion, invasiveness, and self-renewal properties in responsive cells [1, 2]. Depending on the cell and tissue type, modulation of these cellular properties by TGFβ superfamily members will regulate different processes ranging from gastrulation to formation of a functional vascular system during embryonic development, as well as organ morphogenesis and homeostasis at various postnatal stages [1]. The TGFβ superfamily is conserved through metazoan evolution and includes TGFβs (1–3), bone morphogenic proteins (BMPs 1–20), growth and differentiation factors (GDFs including myostatin), activins (A and B), inhibins (A and B), nodal, leftys (1 and 2), and Mullerian inhibiting substances (MIS) [2]. The TGFβ family, the focus of this review, comprises three different isoforms encod
