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The Differentiation and Function of Myofibroblasts is Regulated by Mast Cell Mediators
Open accessAbstract
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.
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“Mast cells also produce tryptase, a serine proteinase, which, remarkably, stimulates fibroblast proliferation and collagen production (142, 160, 161), and histamine, which also”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [142]
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Metadata
- Authors
- Gailit, J., Marchese, M. J., Kew, R. R., & Gruber, B. L.
- Affiliations
- Northport VA Medical Center (US)
- State University of New York (US)
- Corresponding author
- Gruber, Barry L.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2001-11
- Volume
- 117
- Issue
- 5
- Pages
- 1113-1119
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2082391434
- Cited by
- 174
- References
- 70
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 11 · 2013: 20 · 2012: 8
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Rheumatology › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- myofibroblasts, mast cells, mast cell mediators, fibroblast differentiation, alpha-smooth muscle actin, collagen gel contraction, tryptase, histamine, TNF-α, HMC-1 cells, dermal fibroblasts, systemic sclerosis, wound healing
- MeSH terms
- Actins, Cell Differentiation, Cell Line, Collagen, Fibroblasts, Histamine, Humans, Mast Cells, Muscle, Smooth, Organ Culture Techniques, Serine Endopeptidases, Tumor Necrosis Factor-alpha, Tryptases
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