Molecular basis for antagonism between PDGF and the TGFβ family of signalling pathways by control of miR‐24 expression
Document Type
Article
Publication Date
2-3-2010
Publisher
Springer Nature
Abstract
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‐β (TGFβ)‐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 TGFβ 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 TGFβ pathways, and its effect on the control of the vSMC phenotype.
Recommended Citation
Chan, M. C., Hilyard, A. C., Wu, C., Davis, B. N., Hill, N. S., Lal, A., Lieberman, J., Lagna, G., & Hata, A. (2010). Molecular basis for antagonism between PDGF and the TGFβ family of signalling pathways by control of miR‐24 expression. The EMBO Journal, 29(3), 559–573. https://doi.org/10.1038/emboj.2009.370
