Feedback inhibition of high TGF-beta1 concentrations on myofibroblast induction and contraction by Dupuytren's fibroblasts.

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.

• 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)

Chemical References

• Transforming Growth Factor beta1

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