Copyright © 2005, European Society of Cardiology
Activation of cardiac and smooth muscle-specific genes in primary human cells after forced expression of human myocardin
aDepartment of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, P.O. Box 9600, 2300 RC Leiden, the Netherlands
bDepartment of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL, Leiden, the Netherlands
cInteruniversity Cardiology Institute of the Netherlands, Catharijnesingel 52, 3511 GC, Utrecht, the Netherlands
* Corresponding author. Tel.: +31 71 5262020; fax: +31 71 5266809. Email address: d.e.atsma{at}lumc.nl
Objective: Myocardin is a recently discovered transcriptional regulator of cardiac and smooth muscle development. Its ability to transactivate smooth muscle-specific genes has been firmly established in animal cells but its effect on heart muscle genes has been investigated less extensively and the consequences of ectopic myocardin expression in human cells are unknown.
Methods: In this study, primary human mesenchymal stem cells and foreskin fibroblasts were transduced with human adenovirus vectors expressing the longest splice variant of the human myocardin gene (hAd5/F50.CMV.myocL) or with control vectors. One week later, the expression of muscle-restricted genes in these cells was analyzed by reverse transcription-polymerase chain reactions and immunofluorescence microscopy.
Results: Forced expression of myocardin induced transcription of cardiac and smooth muscle genes in both cell types but did not lead to activation of skeletal muscle-specific genes. Double labeling experiments using monoclonal antibodies directed against striated (i.e. sarcomeric 
-actin and sarcomeric -actinin) and cardiac (i.e. natriuretic peptide precursor A) muscle-specific proteins together with a polyclonal antiserum specific for smooth muscle myosin heavy chain revealed that hAd5/F50.CMV.myocL-transduced cells co-express heart and smooth muscle-specific genes.
Conclusions: These data indicate that the myocardin protein is a strong inducer of both smooth and cardiac muscle genes, but that additional factors are necessary to fully commit cells to either cardiac or smooth muscle cell fates.
KEYWORDS Cell differentiation; Myocardin; Myocyte; Smooth muscle; Stem cells
Time for primary review 17 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Long, D. L. Tharp, M. A. Georger, O. J. Slivano, M. Y. Lee, B. R. Wamhoff, D. K. Bowles, and J. M. Miano The Smooth Muscle Cell-restricted KCNMB1 Ion Channel Subunit Is a Direct Transcriptional Target of Serum Response Factor and Myocardin J. Biol. Chem., November 27, 2009; 284(48): 33671 - 33682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Perot, J. Derre, J.-M. Coindre, F. Tirode, C. Lucchesi, O. Mariani, L. Gibault, L. Guillou, P. Terrier, and A. Aurias Strong Smooth Muscle Differentiation Is Dependent on Myocardin Gene Amplification in Most Human Retroperitoneal Leiomyosarcomas Cancer Res., March 15, 2009; 69(6): 2269 - 2278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Meadows, A. S. Warkman, M. C. Salanga, E. M. Small, and P. A. Krieg The myocardin-related transcription factor, MASTR, cooperates with MyoD to activate skeletal muscle gene expression PNAS, February 5, 2008; 105(5): 1545 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Pijnappels, J. van Tuyn, A. A.F. de Vries, R. W. Grauss, A. van der Laarse, D. L. Ypey, D. E. Atsma, and M. J. Schalij Resynchronization of Separated Rat Cardiomyocyte Fields With Genetically Modified Human Ventricular Scar Fibroblasts Circulation, October 30, 2007; 116(18): 2018 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. van Tuyn, D. A. Pijnappels, A. A. F. de Vries, I. de Vries, I. van der Velde-van Dijke, S. Knaan-Shanzer, A. van der Laarse, M. J. Schalij, and D. E. Atsma Fibroblasts from human postmyocardial infarction scars acquire properties of cardiomyocytes after transduction with a recombinant myocardin gene FASEB J, October 1, 2007; 21(12): 3369 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, A. Li, Z. Wang, X. Feng, E. N. Olson, and R. J. Schwartz Myocardin Sumoylation Transactivates Cardiogenic Genes in Pluripotent 10T1/2 Fibroblasts Mol. Cell. Biol., January 15, 2007; 27(2): 622 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, Y. C. Bae, J. S. Jung, and J. H. Kim Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-{beta}-dependent mechanism J. Cell Sci., December 1, 2006; 119(23): 4994 - 5005. [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]
|
|
|
|
 |
|
 D. A. Pijnappels, M. J. Schalij, J. van Tuyn, D. L. Ypey, A. A.F. de Vries, E. E. van der Wall, A. van der Laarse, and D. E. Atsma Progressive increase in conduction velocity across human mesenchymal stem cells is mediated by enhanced electrical coupling Cardiovasc Res, November 1, 2006; 72(2): 282 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.C. T. Pipes, E. E. Creemers, and E. N. Olson The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes & Dev., June 15, 2006; 20(12): 1545 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Konhilas and L. A. Leinwand Partnering Up for Cardiac Hypertrophy Circ. Res., April 28, 2006; 98(8): 985 - 987. [Full Text] [PDF]
|
|
|
|
|
|
H. M. Piper and E. A. Martinson Cardiovascular Research speeds up-Even more Cardiovasc Res, March 1, 2006; 69(4): 773 - 776. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A.F.V. Goncalves, A. A.F. de Vries, M. Holkers, M. J.M. van de Watering, I. van der Velde, G. P. van Nierop, D. Valerio, and S. Knaan-Shanzer Human mesenchymal stem cells ectopically expressing full-length dystrophin can complement Duchenne muscular dystrophy myotubes by cell fusion Hum. Mol. Genet., January 15, 2006; 15(2): 213 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ventura Forced myocardin expression primes cardiac and smooth muscle transcription patterning in human mesenchymal stem cells Cardiovasc Res, August 1, 2005; 67(2): 182 - 183. [Full Text] [PDF]
|
|