Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-β
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.
|Keywords||Activin A, Extracellular matrix, Smad1, Smad2, Transforming growth factor-β (TGF-β), Vascular smooth muscle cells|
|Persistent URL||dx.doi.org/10.1016/j.yexcr.2010.10.007, hdl.handle.net/1765/33542|
Groenendijk, B.C.W., Benus, G.F.J.D., Klous, A., Pacheco, Y.M., Volger, O.L., Fledderus, J.O., … de Vries, C.J.M.. (2011). Activin A induces a non-fibrotic phenotype in smooth muscle cells in contrast to TGF-β. Experimental Cell Research: emphasizing molecular approaches to cell biology, 317(2), 131–142. doi:10.1016/j.yexcr.2010.10.007