TY - JOUR
T1 - Myocardin induces cardiomyocyte hypertrophy
AU - Xing, Weibing
AU - Zhang, Tong Cun
AU - Cao, Dongsun
AU - Wang, Zhigao
AU - Antos, Christopher L.
AU - Li, Shijie
AU - Wang, Yibin
AU - Olson, Eric N.
AU - Wang, Da Zhi
PY - 2006/4
Y1 - 2006/4
N2 - In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly of sarcomeres, and cellular enlargement. We show that hypertrophic signals stimulate the expression and transcriptional activity of myocardin, a cardiac and smooth muscle-specific coactivator of serum response factor (SRF). Consistent with a role for myocardin as a transducer of hypertrophic signals, forced expression of myocardin in cardiomyocytes is sufficient to substitute for hypertrophic signals and induce cardiomyocyte hypertrophy and the fetal cardiac gene program. Conversely, a dominant-negative mutant form of myocardin, which retains the ability to associate with SRF but is defective in transcriptional activation, blocks cardiomyocyte hypertrophy induced by hypertrophic agonists such as phenylephrine and leukemia inhibitory factor. Myocardin-dependent hypertrophy can also be partially repressed by histone deacetylase 5, a transcriptional repressor of myocardin. These findings identify myocardin as a nuclear effector of hypertrophic signaling pathways that couples stress signals to a transcriptional program for postnatal cardiac growth and remodeling.
AB - In response to stress signals, postnatal cardiomyocytes undergo hypertrophic growth accompanied by activation of a fetal gene program, assembly of sarcomeres, and cellular enlargement. We show that hypertrophic signals stimulate the expression and transcriptional activity of myocardin, a cardiac and smooth muscle-specific coactivator of serum response factor (SRF). Consistent with a role for myocardin as a transducer of hypertrophic signals, forced expression of myocardin in cardiomyocytes is sufficient to substitute for hypertrophic signals and induce cardiomyocyte hypertrophy and the fetal cardiac gene program. Conversely, a dominant-negative mutant form of myocardin, which retains the ability to associate with SRF but is defective in transcriptional activation, blocks cardiomyocyte hypertrophy induced by hypertrophic agonists such as phenylephrine and leukemia inhibitory factor. Myocardin-dependent hypertrophy can also be partially repressed by histone deacetylase 5, a transcriptional repressor of myocardin. These findings identify myocardin as a nuclear effector of hypertrophic signaling pathways that couples stress signals to a transcriptional program for postnatal cardiac growth and remodeling.
KW - Cardiac hypertrophy
KW - Cardiac myocytes
KW - Cardiac transcription factors
KW - Myocardin
KW - Serum response factor
KW - Transcription factors
KW - Transcriptional regulation
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U2 - 10.1161/01.RES.0000218781.23144.3e
DO - 10.1161/01.RES.0000218781.23144.3e
M3 - Article
C2 - 16556869
AN - SCOPUS:33646798121
SN - 0009-7330
VL - 98
SP - 1089
EP - 1097
JO - Circulation research
JF - Circulation research
IS - 8
ER -