Myocardin induces cardiomyocyte hypertrophy

Weibing Xing, Tong Cun Zhang, Dongsun Cao, Zhigao Wang, Christopher L. Antos, Shijie Li, Yibin Wang, Eric N. Olson, Da Zhi Wang

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1089-1097
Number of pages9
JournalCirculation Research
Volume98
Issue number8
DOIs
StatePublished - Apr 2006

Fingerprint

Cardiac Myocytes
Hypertrophy
Serum Response Factor
Leukemia Inhibitory Factor
Sarcomeres
Histone Deacetylases
Cardiomegaly
Phenylephrine
Growth
myocardin
Transducers
Transcriptional Activation
Genes
Smooth Muscle
Myocardium

Keywords

  • Cardiac hypertrophy
  • Cardiac myocytes
  • Cardiac transcription factors
  • Myocardin
  • Serum response factor
  • Transcription factors
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Xing, W., Zhang, T. C., Cao, D., Wang, Z., Antos, C. L., Li, S., ... Wang, D. Z. (2006). Myocardin induces cardiomyocyte hypertrophy. Circulation Research, 98(8), 1089-1097. https://doi.org/10.1161/01.RES.0000218781.23144.3e

Myocardin induces cardiomyocyte hypertrophy. / Xing, Weibing; Zhang, Tong Cun; Cao, Dongsun; Wang, Zhigao; Antos, Christopher L.; Li, Shijie; Wang, Yibin; Olson, Eric N.; Wang, Da Zhi.

In: Circulation Research, Vol. 98, No. 8, 04.2006, p. 1089-1097.

Research output: Contribution to journalArticle

Xing, W, Zhang, TC, Cao, D, Wang, Z, Antos, CL, Li, S, Wang, Y, Olson, EN & Wang, DZ 2006, 'Myocardin induces cardiomyocyte hypertrophy', Circulation Research, vol. 98, no. 8, pp. 1089-1097. https://doi.org/10.1161/01.RES.0000218781.23144.3e
Xing, Weibing ; Zhang, Tong Cun ; Cao, Dongsun ; Wang, Zhigao ; Antos, Christopher L. ; Li, Shijie ; Wang, Yibin ; Olson, Eric N. ; Wang, Da Zhi. / Myocardin induces cardiomyocyte hypertrophy. In: Circulation Research. 2006 ; Vol. 98, No. 8. pp. 1089-1097.
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