Abstract
Transforming growth factor-β (TGF-β) is a multifunctional cytokine with important roles in embryogenesis and maintaining tissue homeostasis during adult life. There are three isoforms of TGF-β, i.e., TGF-β1, -β2, and -β3, which signal by binding to a complex of transmembrane type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. In most cell types TGF-β signals via TGF-β type II receptor (TβRII) and TβRI, also termed activin receptor-like kinase 5 (ALK5). In endothelial cells, TGF-β signals via ALK5 and ALK1. These two type I receptors mediate opposite cellular response for TGF-β. The co-receptor endoglin, highly expressed on proliferating endothelial cells, facilitates TGF-β/ALK1 and inhibits TGF-β/ALK5 signaling. Knockout of TGF-β receptors in mice all result in embryonic lethality during midgestation from defects in angiogenesis, illustrating the pivotal role of TGF-β in this process. This chapter introduces methods for examining the function and regulation of TGF-β in angiogenesis in in vitro assays using cultured endothelial cells and ex vivo metatarsal explants.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364
Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307
Goumans M-J, Valdimarsdottir G, Itoh S et al (2002) Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors. EMBO J 21:1743–1753
Goumans M-J, Liu Z, ten Dijke P (2009) TGF-beta signaling in vascular biology and dysfunction. Cell Res 19:116–127
Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577–584
ten Dijke P, Hill CS (2004) New insights into TGF-beta-Smad signalling. Trends Biochem Sci 29:265–273
Cunha SI, Pardali E, Thorikay M et al (2010) Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis. J Exp Med 207:85–100
Jakobsson L, Kreuger J, Claesson-Welsh L (2007) Building blood vessels–stem cell models in vascular biology. J Cell Biol 177:751–755
Liu Z, Kobayashi K, van Dinther M et al (2009) VEGF and inhibitors of TGFbeta type-I receptor kinase synergistically promote blood-vessel formation by inducing alpha5-integrin expression. J Cell Sci 122:3294–3302
Zwijsen A, Goumans MJ, Lawson KA et al (1999) Ectopic expression of the transforming growth factor beta type II receptor disrupts mesoderm organisation during mouse gastrulation. Dev Dyn 214:141–151
Goumans MJ, Ward-van Oostwaard D, Wianny F et al (1998) Mouse embryonic stem cells with aberrant transforming growth factor beta signalling exhibit impaired differentiation in vitro and in vivo. Differentiation 63:101–113
Acknowledgements
Our studies on the role of TGF-β receptors in tumor angiogenesis and other diseases are supported by the TAS ZonMW grant, the Dutch Cancer Society, Netherlands Research Council, Le Ducq Foundation, The Netherlands Institute for Regenerative Medicine (NIRM), Cancer Genomics Centre Netherlands, and Centre for Biomedical Genetics.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Maring, J.A., van Meeteren, L.A., Goumans, M.J., ten Dijke, P. (2016). Interrogating TGF-β Function and Regulation in Endothelial Cells. In: Feng, XH., Xu, P., Lin, X. (eds) TGF-β Signaling. Methods in Molecular Biology, vol 1344. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2966-5_11
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2966-5_11
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2965-8
Online ISBN: 978-1-4939-2966-5
eBook Packages: Springer Protocols