Myocardin-related transcription factors A and B are key regulators of TGF-β1-induced fibroblast to myofibroblast differentiation

J Invest Dermatol. 2011 Dec;131(12):2378-85. doi: 10.1038/jid.2011.219. Epub 2011 Jul 21.


Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor β-1 (TGF-β1) helps facilitate the differentiation of fibroblasts into myofibroblasts, but the exact mechanism by which this differentiation occurs, in response to TGF-β1, remains unclear. Myocardin-related transcription factors A and B (MRTFs, MRTF-A/B) are transcriptional co-activators that regulate the expression of smooth muscle-specific cytoskeletal proteins, including SMαA, in smooth muscle cells and fibroblasts. In this study, we demonstrate that TGF-β1 mediates myofibroblast differentiation and the expression of a contractile gene program through the actions of the MRTFs. Transient transfection of a constitutively active MRTF-A induced an increase in the expression of SMαA and other smooth muscle-specific cytoskeletal proteins, and an increase in myofibroblast contractility, even in the absence of TGF-β1. MRTF-A/B knockdown, in TGF-β1-differentiated myofibroblasts, resulted in decreased smooth muscle-specific cytoskeletal protein expression levels and reduced contractile force generation, as well as a decrease in focal adhesion size and number. These results provide direct evidence that the MRTFs are mediators of myofibroblast differentiation in response to TGF-β1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Differentiation / genetics*
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Focal Adhesions / metabolism
  • Myofibroblasts / cytology*
  • Myofibroblasts / metabolism
  • Rats
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1 / metabolism*


  • Actins
  • Cytoskeletal Proteins
  • Tgfb1 protein, rat
  • Transcription Factors
  • Transforming Growth Factor beta1
  • myocardin-related transcription factor-A, rat
  • myocardin-related transcription factor-B, rat
  • smooth muscle actin, rat