Published online before print March 11, 2004, doi: 10.1161/01.RES.0000125622.46280.95
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 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
This article has been cited by other articles:
 |
|
 |
|
  H. P. Makarenkova, K. N. Gonzalez, W. B. Kiosses, and R. Meech Barx2 Controls Myoblast Fusion and Promotes MyoD-mediated Activation of the Smooth Muscle{alpha}-Actin Gene J. Biol. Chem., May 29, 2009; 284(22): 14866 - 14874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Xie, Y. Fan, H. Zhang, Y. Zhang, M. She, D. Gu, C. Patterson, and H. Li CHIP Represses Myocardin-Induced Smooth Muscle Cell Differentiation via Ubiquitin-Mediated Proteasomal Degradation Mol. Cell. Biol., May 1, 2009; 29(9): 2398 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shang, T. Yoshida, B. A. Amendt, J. F. Martin, and G. K. Owens Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation J. Cell Biol., October 14, 2008; 181(3): 461 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Jiang and B. Stefanovic Homeobox Gene Prx1 Is Expressed in Activated Hepatic Stellate Cells and Transactivates Collagen {alpha}1(I) Promoter Exp Biol Med, March 1, 2008; 233(3): 286 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Xu, C.-H. Ha, C. Wong, W. Wang, A. Hausser, K. Pfizenmaier, E. N. Olson, T. A. McKinsey, and Z.-G. Jin Angiotensin II Stimulates Protein Kinase D-Dependent Histone Deacetylase 5 Phosphorylation and Nuclear Export Leading to Vascular Smooth Muscle Cell Hypertrophy Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2355 - 2362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. G. McDonald and G. K. Owens Programming Smooth Muscle Plasticity With Chromatin Dynamics Circ. Res., May 25, 2007; 100(10): 1428 - 1441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jin, M. J. Kern, C. A. Otey, B. R. Wamhoff, and A. V. Somlyo Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and its Newly Identified Binding Partner Palladin to Promote Cell Migration Circ. Res., March 30, 2007; 100(6): 817 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kawai-Kowase and G. K. Owens Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 2007; 292(1): C59 - C69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Herring, O. El-Mounayri, P. J. Gallagher, F. Yin, and J. Zhou Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues Am J Physiol Cell Physiol, November 1, 2006; 291(5): C817 - C827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Han, W.-Y. Hu, O. Chernaya, N. Antic, L. Gu, M. Gupta, M. Piano, and P. de Lanerolle Increased Myosin Light Chain Kinase Expression in Hypertension: Regulation by Serum Response Factor via an Insertion Mutation in the Promoter Mol. Biol. Cell, September 1, 2006; 17(9): 4039 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Yin, A. M. Hoggatt, J. Zhou, and B. P. Herring 130-kDa smooth muscle myosin light chain kinase is transcribed from a CArG-dependent, internal promoter within the mouse mylk gene Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1599 - C1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Wamhoff, D. K. Bowles, and G. K. Owens Excitation-Transcription Coupling in Arterial Smooth Muscle Circ. Res., April 14, 2006; 98(7): 868 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gorenne, L. Jin, T. Yoshida, J.M. Sanders, I.J. Sarembock, G.K. Owens, A.P. Somlyo, and A.V. Somlyo LPP Expression During In Vitro Smooth Muscle Differentiation and Stent-Induced Vascular Injury Circ. Res., February 17, 2006; 98(3): 378 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Qiu, R. P. Ritchie, Z. Fu, D. Cao, J. Cumming, J. M. Miano, D.-Z. Wang, H. J. Li, and L. Li Myocardin Enhances Smad3-Mediated Transforming Growth Factor-{beta}1 Signaling in a CArG Box-Independent Manner: Smad-Binding Element Is an Important cis Element for SM22{alpha} Transcription In Vivo Circ. Res., November 11, 2005; 97(10): 983 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawai-Kowase, M. S. Kumar, M. H. Hoofnagle, T. Yoshida, and G. K. Owens PIAS1 Activates the Expression of Smooth Muscle Cell Differentiation Marker Genes by Interacting with Serum Response Factor and Class I Basic Helix-Loop-Helix Proteins Mol. Cell. Biol., September 15, 2005; 25(18): 8009 - 8023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, S. Sinha, O. G. McDonald, Y. Shang, M. H. Hoofnagle, and G. K. Owens Kruppel-like Factor 4 Abrogates Myocardin-induced Activation of Smooth Muscle Gene Expression J. Biol. Chem., March 11, 2005; 280(10): 9719 - 9727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshida and G. K. Owens Molecular Determinants of Vascular Smooth Muscle Cell Diversity Circ. Res., February 18, 2005; 96(3): 280 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yoshida, K. Kawai-Kowase, and G. K. Owens Forced Expression of Myocardin Is Not Sufficient for Induction of Smooth Muscle Differentiation in Multipotential Embryonic Cells Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1596 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.R. Wamhoff, D.K. Bowles, O.G. McDonald, S. Sinha, A.P. Somlyo, A.V. Somlyo, and G.K. Owens L-type Voltage-Gated Ca2+ Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF-Dependent Mechanism Circ. Res., August 20, 2004; 95(4): 406 - 414. [Abstract] [Full Text] [PDF]
|
|