Myocardin is sufficient for a smooth muscle-like contractile phenotype.
BACKGROUND
Myocardin (Myocd) is a strong coactivator that binds the serum response factor (SRF) transcription factor over CArG elements embedded within smooth muscle cell (SMC) and cardiac muscle cyto-contractile genes. Here, we sought to ascertain whether Myocd-mediated gene expression confers a structural and physiological cardiac or SMC phenotype.


RESULTS
Adenoviral-mediated expression of Myocd in the BC(3)H1 cell line induces cardiac and SMC genes while suppressing both skeletal muscle markers and cell growth. Immunofluorescence microscopy shows that SRF and a SMC-like cyto-contractile apparatus are elevated with Myocd overexpression. A short hairpin RNA to Srf impairs BC(3)H1 cyto-architecture; however, cotransduction with Myocd results in complete restoration of the cyto-architecture. Electron microscopic studies demonstrate a SMC ultrastructural phenotype with no evidence for cardiac sarcomerogenesis. Biochemical and time-lapsed videomicroscopy assays reveal clear evidence for Myocd-induced SMC-like contraction.


CONCLUSIONS
Myocd is sufficient for the establishment of a SMC-like contractile phenotype.
Long
Xiaochun
X
Aab Cardiovascular Research Institute, University of Rochester School of Medicine & Dentistry, 211 Bailey Road, Rochester, New York 14586, USA.
Bell
Robert D
RD
Gerthoffer
William T
WT
Zlokovic
Berislav V
BV
Miano
Joseph M
JM
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D009687:Nuclear Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D000099251:Myocardin
D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin