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Groenendijk, B.C.W.; Benus, G.F.J.D.; Klous, A.; Pacheco, Y.M.; Volger, O.L.; Fledderus, J.O.; ... ; Vries, C.J.M. de (2011)

Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-beta

Article / Letter to editor
Aims: Activin A and transforming growth factor-beta (TGF-beta) belong to the same family of growth and differentiation factors that modulate vascular lesion formation in distinct ways, which we wish to understand mechanistically. Methods and results: We investigated the expression of cell-surface receptors and activation of Smads in human vascular smooth muscle cells (SMCs) and demonstrated that activin receptor-like kinase-1 (ALK-1), ALK-4, ALK-5 and endoglin are expressed in human SMCs. As expected, TGF-beta 1 activates Smad1 and Smad2 in these cells. Interestingly, activin A also induces phosphorylation of both Smads, which has not been reported for Smad1 before. Transcriptome analyses of activin A and TGF-beta 1 treated SMCs with subsequent Gene-Set Enrichment Analyses revealed that many downstream gene networks are induced by both factors. However, the effect of activin A on expression kinetics of individual genes is less pronounced than for TGF-beta 1, which is explained by a...Show moreAims: Activin A and transforming growth factor-beta (TGF-beta) belong to the same family of growth and differentiation factors that modulate vascular lesion formation in distinct ways, which we wish to understand mechanistically. Methods and results: We investigated the expression of cell-surface receptors and activation of Smads in human vascular smooth muscle cells (SMCs) and demonstrated that activin receptor-like kinase-1 (ALK-1), ALK-4, ALK-5 and endoglin are expressed in human SMCs. As expected, TGF-beta 1 activates Smad1 and Smad2 in these cells. Interestingly, activin A also induces phosphorylation of both Smads, which has not been reported for Smad1 before. Transcriptome analyses of activin A and TGF-beta 1 treated SMCs with subsequent Gene-Set Enrichment Analyses revealed that many downstream gene networks are induced by both factors. However, the effect of activin A on expression kinetics of individual genes is less pronounced than for TGF-beta 1, which is explained by a more rapid dephosphorylation of Smads and p38-MAPK in response to activin A. Substantial differences in expression of fibronectin, alpha-v integrin and total extracellular collagen synthesis were observed. Conclusions: Genome-wide mRNA expression analyses clarify the distinct modulation of vascular lesion formation by activin A and TGF-beta 1, most significantly because activin A is non-fibrotic. (C) 2010 Elsevier Inc. All rights reserved.Show less
Activin A Transforming growth factor-beta (TGF-beta) Vascular smooth muscle cells Smad1 Smad2 Extracellular matrix growth-factor-beta atherosclerotic lesions i receptors expression gene hyperplasia activation protein identification proliferation
All authors
Groenendijk, B.C.W.; Benus, G.F.J.D.; Klous, A.; Pacheco, Y.M.; Volger, O.L.; Fledderus, J.O.; Ferreira, V.; Engelse, M.A.; Pannekoek, H.; Dijke, P. ten; Horrevoets, A.J.G.; Vries, C.J.M. de
Date
2011-01-15
Journal
Experimental Cell Research
Volume
317
Issue
2
Pages
131 - 142
DOI
doi:10.1016/j.yexcr.2010.10.007