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Updated: Jul 16, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Signaling by ALK5 mediates TGF-beta-induced ET-1 expression in endothelial cells: a role for migration and
Cristina Castañares1, Mariano Redondo-Horcajo, Noemi Magán-Marchal
1Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Instituto Reina Sofía de Investigaciones Nefrológicas, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Abstract:
Endothelin-1 (ET-1) is a potent endothelial-derived 21-amino-acid vasoconstrictor peptide and its expression is potently regulated by the cytokine transforming growth factor-beta (TGF-beta). Most cell types contain a TGF-beta type I receptor form known as activin receptor-like kinase 5 (ALK5). However, endothelial cells coexpress an additional type I receptor named ALK1. These forms do not constitute redundant receptors with the same function, but they activate different Smad-mediated expression programmes leading to specific endothelial phenotypes. The aim of our study was to characterize the TGF-beta-induced pathway leading to ET-1 expression in endothelial cells and the contribution of the TGF-beta-mediated enhancement of ET-1 to the regulation of the endothelial cell migration and proliferation capacity. Our experiments indicate that TGF-beta induces ET-1 expression preferentially through the ALK5/Smad3 pathway. Specific ALK5 inhibition totally blocked the anti-angiogenic effect of TGF-beta. Antagonism of ET receptors partially reverted the effect of TGF-beta, indicating that a significant portion of the anti-migratory and anti-proliferative actions of this cytokine is mediated by ET-1 acting in an autocrine manner on endothelial cells.
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