MMP-2 expression by fibroblasts is suppressed by the myofibroblast phenotype

Exp Cell Res. 2012 Aug 1;318(13):1542-53. doi: 10.1016/j.yexcr.2012.03.007. Epub 2012 Mar 17.


During wound healing, fibroblasts transition from quiescence to a migratory state, then to a contractile myofibroblast state associated with wound closure. We found that the myofibroblast phenotype, characterized by the expression of high levels of contractile proteins, suppresses the expression of the pro-migratory gene, MMP-2. Fibroblasts cultured in a 3-D collagen lattice and allowed to develop tension showed increased contractile protein expression and decreased MMP-2 levels in comparison to a stress-released lattice. In 2-D cultures, factors that promote fibroblast contractility, including serum or TGF-β, down-regulated MMP-2. Pharmacologically inducing F-actin disassembly or reduced contractility increased MMP-2 expression, while conditions that promote F-actin assembly suppressed MMP-2 expression. In all cases, changes in MMP-2 levels were inversely related to changes in the contractile marker, smooth muscle α-actin. To determine if the mechanisms involved in contractile protein gene expression play a direct role in MMP-2 regulation, we used RNAi-mediated knock-down of the myocardin-like factors, MRTF-A and MRTF-B, which induced the down-regulation of contractile protein genes by fibroblasts under both serum-containing and serum-free conditions. In the presence of serum or TGF-β, MRTF-A/B knock-down resulted in the up-regulation of MMP-2; serum-free conditions prevented this increased expression. Together, these results indicate that, while MMP-2 expression is suppressed by F-actin formation, its up-regulation is not simply a consequence of contractile protein down-regulation.

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Animals
  • Cell Culture Techniques / methods
  • Cell Line
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Fibroblasts / cytology
  • Fibroblasts / enzymology*
  • Fibroblasts / physiology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Knockdown Techniques
  • Insulin-Like Growth Factor I / pharmacology
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism*
  • Models, Biological
  • Myofibroblasts / cytology
  • Myofibroblasts / enzymology*
  • Myofibroblasts / physiology
  • Phenotype
  • Protein Multimerization
  • RNA Interference
  • Rats
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Wound Healing / genetics
  • Wound Healing / physiology


  • Actins
  • Transcription Factors
  • myocardin-related transcription factor-A, rat
  • myocardin-related transcription factor-B, rat
  • smooth muscle actin, rat
  • Insulin-Like Growth Factor I
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat