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Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice.
- Source :
-
EMBO Journal . 11/28/2012, Vol. 31 Issue 23, p4428-4440. 13p. - Publication Year :
- 2012
-
Abstract
- Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE?/? mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1?/?) mice and atherosclerotic lesions in Mkl1?/?; ApoE?/? mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin ?1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1?/? mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02614189
- Volume :
- 31
- Issue :
- 23
- Database :
- Academic Search Index
- Journal :
- EMBO Journal
- Publication Type :
- Academic Journal
- Accession number :
- 83621645
- Full Text :
- https://doi.org/10.1038/emboj.2012.296