Transforming growth factor β and platelet-derived growth factor modulation of myofibroblast development from corneal fibroblasts in vitro
Open accessAbstract
The purpose of this study was to test the hypotheses that development of mature vimentin+/α-smooth muscle actin+/desmin+ (V+A+D+) myofibroblasts from corneal fibroblasts is regulated by transforming growth factor (TGF) β and platelet-derived growth factor (PDGF); and that myofibroblast development in vitro follows a similar developmental pathway as it does in vivo. Mouse corneal stromal fibroblasts (MSF) were isolated from the corneas of Swiss Webster mice and cultured in serum-free media augmented with DMEM/F12 and varying doses of TGFβ (0.1-2.0 ng/ml), with and without mouse PDGF-AA and/or PDGF-BB (2.0 ng/ml), to study the transition of the MSF to V+A+D+ myofibroblasts. The mean percentage of vimentin+, α-SMA+ and desmin+ cells was determined at each time point (2-15 days), with each growth factor concentration. MSF in vitro were noted to undergo the same developmental transition from V+A-D- to V+A+D- to V+A+D+ myofibroblasts as precursors undergo in vivo. TGFβ at a dose of 0.5 ng/ml and 1.0 ng/ml with 2.0 ng/ml PDGF-AA and 2.0 ng/ml PDGF-BB in DMEM/F12 serum-free media was optimal for the development of V+A+D+ myofibroblasts. This study defines optimal in vitro conditions to monitor the development of MSF into myofibroblasts. The combined effects of TGFβ and PDGF promote the full development of V+A+D+ myofibroblasts from MSF.
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Co-stimulation of mouse corneal stromal fibroblasts with TGFβ and PDGF greatly enhances myofibroblast formation compared to TGFβ alone.
“TGFβ and PDGF can work in concert, for example, in mouse corneal stromal fibroblasts co-stimulation of fibroblasts with TGFβ and PDGF greatly enhances myofibroblast formation compared to TGFβ alone (61).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [61]
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- Authors
- Singh, V., Barbosa, F. L., Torricelli, A. A. M., Santhiago, M. R., & Wilson, S. E.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Wilson, Steven E.
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 120
- Pages
- 152-160
- ISSN
- 0014-4835 (ISSN-L)
- PMC
- PMC3943625
- OpenAlex
- W1980646240
- Cited by
- 55
- References
- 27
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- US Public Health Service (EY10056, EY015638)
- National Eye Institute, National Institutes of Health
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- myofibroblast differentiation, corneal fibroblasts, corneal stromal fibroblasts, TGF-beta, platelet-derived growth factor, PDGF-AA, PDGF-BB, vimentin, alpha-smooth muscle actin, desmin, corneal fibrosis
- MeSH terms
- Becaplermin, Actins, Animals, Cell Differentiation, Cells, Cultured, Corneal Stroma, Desmin, Drug Combinations, Immunohistochemistry, Platelet-Derived Growth Factor, Vimentin, Transforming Growth Factor beta, Proto-Oncogene Proteins c-sis, Mice, Myofibroblasts, Corneal Keratocytes
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