Abstract |
Myofibroblasts and TGF-beta1 are implicated in Dupuytren's contracture. Transforming growth fact- or beta1(TGF-beta1) (1-10ng/ml) increases myofibroblast induction in Dupuytren's fibroblasts and contraction in a collagen model. However, higher doses (20-30ng/ml) inhibit contraction in dermal fibroblasts. We hypothesized higher doses of TGF-beta1 would inhibit induction of myofibroblasts and contraction by Dupuytren's fibroblasts. Increasing doses of TGF-beta1 (0-30ng/ml) were tested on Dupuytren's fibroblasts using immunofluorescence to determine myofibroblast upregulation and a 3D collagen model used to determine contractile forces. Flexor retinaculum fibroblasts were used as controls. TGF-beta1 induced myofibroblasts in Dupuytren's fibroblasts (n=3) from 12% (0ng/ml) to 23% (12.5ng/ml) at 24 hours but dropped to 13% at 30ng/ml (P<0.05). This response was mirrored in the contraction profiles. These trends were similar for flexor retinaculum fibroblasts (n=3), but contractile forces and myofibroblast induction were significantly less (P<0.001). This is the first report of negative feedback inhibition of TGF-beta1 at higher concentrations in Dupuytren's fibroblasts.
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Authors | M Wong, V Mudera |
Journal | Journal of hand surgery (Edinburgh, Scotland)
(J Hand Surg Br)
Vol. 31
Issue 5
Pg. 473-83
(Oct 2006)
ISSN: 0266-7681 [Print] Scotland |
PMID | 16875762
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Transforming Growth Factor beta1
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Topics |
- Cells, Cultured
- Dose-Response Relationship, Drug
- Dupuytren Contracture
(metabolism, pathology)
- Feedback, Physiological
(drug effects)
- Fibroblasts
(drug effects, metabolism)
- Humans
- Microscopy, Fluorescence
- Muscle, Skeletal
(metabolism, pathology)
- Transforming Growth Factor beta1
(administration & dosage)
- Up-Regulation
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