Journal
EMBO JOURNAL
Volume 29, Issue 3, Pages 559-573Publisher
WILEY
DOI: 10.1038/emboj.2009.370
Keywords
BMP; microRNA; PDGF; TGF beta; vascular smooth-muscle cell
Categories
Funding
- National Institutes of Health [HD042149, HL082854, HL086572]
- American Heart Association
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Modulation of the vascular smooth-muscle-cell (vSMC) phenotype from a quiescent 'contractile' phenotype to a proliferative 'synthetic' phenotype has been implicated in vascular injury repair, as well as pathogenesis of vascular proliferative diseases. Both bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF beta)-signalling pathways promote a contractile phenotype, while the platelet-derived growth factor-BB (PDGF-BB)-signalling pathway promotes a switch to the synthetic phenotype. Here we show that PDGF-BB induces microRNA-24 (miR-24), which in turn leads to downregulation of Tribbles-like protein-3 (Trb3). Repression of Trb3 coincides with reduced expression of Smad proteins and decrease in BMP and TGF beta signalling, promoting a synthetic phenotype in vSMCs. Inhibition of miR-24 by antisense oligonuclotides abrogates the downregulation of Trb3 as well as pro-synthetic activity of the PDGF-signalling pathway. Thus, this study provides a molecular basis for the antagonism between the PDGF and TGF beta pathways, and its effect on the control of the vSMC phenotype. The EMBO Journal (2010) 29, 559-573. doi:10.1038/emboj.2009.370; Published online 17 December 2009
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