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Journal of Cardiovascular Translational Research

, Volume 5, Issue 6, pp 794–804 | Cite as

The Actin–MRTF–SRF Gene Regulatory Axis and Myofibroblast Differentiation

  • Eric M. Small
Article

Abstract

Cardiac fibroblasts are responsible for necrotic tissue replacement and scar formation after myocardial infarction (MI) and contribute to remodeling in response to pathological stimuli. This response to insult or injury is largely due to the phenotypic plasticity of fibroblasts. When fibroblasts encounter environmental disturbances, whether biomechanical or humoral, they often transform into smooth muscle-like, contractile cells called “myofibroblasts.” The signals that control myofibroblast differentiation include the transforming growth factor (TGF)-β1–Smad pathway and Rho GTPase-dependent actin polymerization. Recent evidence implicates serum response factor (SRF) and the myocardin-related transcription factors (MRTFs) as key mediators of the contractile gene program in response to TGF-β1 or RhoA signaling. This review highlights the function of myofibroblasts in cardiac remodeling and the role of the actin–MRTF–SRF signaling axis in regulating this process.

Keywords

Fibroblast Myofibroblast Actin Serum response factor Myocardin-related transcription factors Fibrosis 

Notes

Acknowledgments

I apologize to the many researchers whose work could not be cited owing to space restrictions. I thank Joe Miano for discussions and comments on the manuscript. This work was funded in part by a Scientist Development Grant from The American Heart Association.

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Aab Cardiovascular Research Institute, Department of Medicine, School of Medicine and DentistryUniversity of RochesterRochesterUSA

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