title: Interrogating TGF-β Function and Regulation in Endothelial Cells.
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.
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands. j.a.maring@lumc.nl.
authors.forename: J A
authors.initials: JA
authors.lastname: Maring
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: van Meeteren
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Goumans
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Centre for Biomedical Genetics, Leiden University Medical Center, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Dijke
mesh_terms: D018929:Cell Culture Techniques; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D018874:Spheroids, Cellular; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Angiogenesis; Endothelial cell; TGF-β; VEGF