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Updated: Mar 31, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Interrogating TGF-β Function and Regulation in Endothelial Cells
J A Maring1, L A van Meeteren2, M J Goumans2
1Department 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.
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.
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