Feedback inhibition of high TGF-β1 concentrations on myofibroblast induction and contraction by Dupuytren's fibroblasts

Myofibroblasts and TGF-beta 1 are implicated in Dupuytren's contracture. Transforming growth factor beta 1(TGF-beta 1) (1-10 ng/ml) increases myofibroblast induction in Dupuytren's fibroblasts and contraction in a collagen model. However, higher doses (20-30 ng/ml) inhibit contraction in dermal fibroblasts. We hypothesized higher doses of TGF-beta 1 would inhibit induction of myotibroblasts and contraction by Dupuytren's fibroblasts. Increasing doses of TGF-PI (0-30 ng/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-PI induced myofibroblasts in Dupuytren's fibroblasts (n = 3) from 12% (0 ng/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-beta 1 at higher concentrations in Dupuytren's fibroblasts.