Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125622.46280.95
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© 2004 American Heart Association, Inc.
Molecular Medicine |
Myocardin and Prx1 Contribute to Angiotensin II-Induced Expression of Smooth Muscle 
-Actin
From the Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Va.
Correspondence to Gary K. Owens, PhD, Department of Molecular Physiology and Biological Physics, University of Virginia, MR5 Room 1220, 415 Lane Road, PO Box 801394, Charlottesville, VA 22908. E-mail gko{at}virginia.edu
Previous studies demonstrated that angiotensin II (Ang II)-induced hypertrophy of smooth muscle cells (SMCs) was associated with increased transcription of SM 
-actin gene. The aim of the present study was to determine whether myocardin, a SMC-selective cofactor of serum response factor (SRF), contributed to Ang II-induced increases in SM -actin transcription. Results showed that Ang II increased myocardin mRNA expression as well as SM -actin mRNA expression via the Ang II type 1 receptor in cultured rat aortic SMCs. Cotransfection studies revealed that CArG elements were required for Ang II-induced transcription of SM -actin gene, and a dominant-negative form of myocardin or a short interfering RNA (siRNA) specific for myocardin decreased Ang II-induced SM -actin transcription. Prx1, a homeodomain protein whose expression was increased by Ang II, also increased SM -actin gene transcription in part via CArG elements, and siRNA specific for Prx1 markedly decreased basal and Ang II-induced SM -actin transcription. Electrophoretic mobility shift assay showed that myocardin and Ang II, respectively, increased formation of a SMC-specific CArG-SRF-myocardin higher order complex. However, Ang II had no effect on binding between myocardin and SRF as determined by a mammalian two-hybrid assay, suggesting that Ang II-induced increases in formation of CArG-SRF-myocardin complex was the result of increased SRF binding to CArG elements and increased myocardin expression. Taken together, these results support a model in which Ang II-induced increases in expression of SM -actin are mediated through Prx1-dependent increases in SRF binding to CArG elements and subsequent recruitment of myocardin.
Key Words: smooth muscle cells • transcriptional coactivator • serum response factor • CArG element • angiotensin II
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