TY - JOUR
T1 - Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-β
AU - Groenendijk, Bianca C. W.
AU - Benus, Germaine F. J. D.
AU - Klous, Anita
AU - Pacheco, Yolanda M.
AU - Volger, Oscar L.
AU - Fledderus, Joost O.
AU - Ferreira, Valerie
AU - Engelse, Marten A.
AU - Pannekoek, Hans
AU - ten Dijke, Peter
AU - Horrevoets, Anton J. G.
AU - de Vries, Carlie J. M.
PY - 2011
Y1 - 2011
N2 - AIMS: Activin A and transforming growth factor-β1 (TGF-β1) 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-β1 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-β1 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-β1, 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-β1, most significantly because activin A is non-fibrotic
AB - AIMS: Activin A and transforming growth factor-β1 (TGF-β1) 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-β1 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-β1 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-β1, 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-β1, most significantly because activin A is non-fibrotic
U2 - https://doi.org/10.1016/j.yexcr.2010.10.007
DO - https://doi.org/10.1016/j.yexcr.2010.10.007
M3 - Article
C2 - 20955695
SN - 0014-4827
VL - 317
SP - 131
EP - 142
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -