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

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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.

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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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  1. Aab Cardiovascular Research Institute, Department of Medicine, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Box CVRI, Rochester, NY, 14642, USA

    Eric M. Small

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Small, E.M. The Actin–MRTF–SRF Gene Regulatory Axis and Myofibroblast Differentiation. J. of Cardiovasc. Trans. Res. 5, 794–804 (2012). https://doi.org/10.1007/s12265-012-9397-0

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