Molecular basis for antagonism between PDGF and the TGF beta family of signalling pathways by control of miR-24 expression

作者：Chan Mun Chun; Hilyard Aaron C; Wu Connie; Davis Brandi N; Hill Nicholas S; Lal Ashish; Lieberman Judy; Lagna Giorgio; Hata Akiko^*

来源：The EMBO Journal, 2010, 29(3): 559-573.

DOI：10.1038/emboj.2009.370

• BMP
• microRNA
• PDGF
• TGF beta
• vascular smooth-muscle cell

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

• 出版日期2010-2-3