Endoglin promotes endothelial cell proliferation and TGF-β/ALK1 signal transduction

Lebrin, Franck, Goumans, Marie-Jose, Jonker, Leon ORCID: https://orcid.org/0000-0001-5867-4663 , Carvalho, Rita LC, Valdimarsdottir, Gudrun, Thorikay, Midory, Mummery, Christine, Arthur, Helen M. and Dijke, Peter ten (2004) Endoglin promotes endothelial cell proliferation and TGF-β/ALK1 signal transduction. The EMBO Journal, 23 (20). pp. 4018-4028.

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Abstract

Endoglin is a transmembrane accessory receptor for transforming growth factor-β (TGF-β) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-β signalling components, is essential during angiogenesis. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-β type I receptor, have been linked to the vascular disorder, hereditary haemorrhagic telangiectasia. However, the function of endoglin in TGF-β/ALK signalling has remained unclear. Here we report that endoglin is required for efficient TGF-β/ALK1 signalling, which indirectly inhibits TGF-β/ALK5 signalling. Endothelial cells lacking endoglin do not grow because TGF-β/ALK1 signalling is reduced and TGF-β/ALK5 signalling is increased. Surviving cells adapt to this imbalance by downregulating ALK5 expression in order to proliferate. The ability of endoglin to promote ALK1 signalling also explains why ectopic endoglin expression in endothelial cells promotes proliferation and blocks TGF-β-induced growth arrest by indirectly reducing TGF-β/ALK5 signalling. Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation.

Item Type:	Article
Journal / Publication Title:	The EMBO Journal
Publisher:	EMBO Press
ISSN:	1460-2075
Departments:	Institute of Health > Medical Sciences
Depositing User:	Insight Administrator
Date Deposited:	21 Jan 2022 09:49
Last Modified:	11 Jan 2024 18:45
URI:	https://insight.cumbria.ac.uk/id/eprint/6346

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