The differentiation and function of myofibroblasts is regulated by mast cell mediators

J Invest Dermatol. 2001 Nov;117(5):1113-9. doi: 10.1046/j.1523-1747.2001.15211.x.


Myofibroblasts are fibroblasts that express certain features of smooth muscle differentiation. Increased numbers of myofibroblasts and mast cells are frequently found together in a wide variety of settings, such as normal wound repair and scleroderma skin, which suggests that mediators produced by the mast cells could play a role in the regulation of myofibroblast differentiation and function. We used a human mast cell line, HMC-1, to determine if mast cells can induce normal human dermal fibroblasts to differentiate into functional myofibroblasts in vitro. We monitored the differentiation process by assaying two properties of the myofibroblast phenotype: expression of alpha-smooth muscle actin and functional capacity to contract a collagen matrix. In both a simple coculture system and in a skin-equivalent culture system, HMC-1 cells induced alpha-smooth muscle actin expression by fibroblasts. HMC-1 cells also stimulated fibroblast contraction of collagen gels, and the relative amount of contraction was dependent upon the number of HMC-1 cells present. To characterize the individual contributions made by specific mast cell products, we examined the effects of histamine, tumor necrosis factor alpha, and tryptase. Histamine induced a clear increase in alpha-smooth muscle actin expression, but it did not appear to stimulate fibroblast contraction. Tumor necrosis factor alpha had no effect in either assay. Purified human tryptase induced alpha-smooth muscle actin expression, and blocking the proteolytic activity of tryptase with specific inhibitors reduced that response. Tryptase inhibitors also eliminated the ability of HMC-1 cells to stimulate fibroblast contraction, suggesting that tryptase secreted by the HMC-1 cells may be one of the active mast cell mediators.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Cell Differentiation / physiology
  • Cell Line
  • Collagen / physiology
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / physiology*
  • Histamine / pharmacology
  • Humans
  • Mast Cells / physiology*
  • Muscle, Smooth / chemistry*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Organ Culture Techniques
  • Serine Endopeptidases / pharmacology
  • Tryptases
  • Tumor Necrosis Factor-alpha / pharmacology


  • Actins
  • Tumor Necrosis Factor-alpha
  • Histamine
  • Collagen
  • Serine Endopeptidases
  • Tryptases