Feedback inhibition of high TGF-beta1 concentrations on myofibroblast induction and contraction by Dupuytren's fibroblasts.
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.
Wong
M
M
Tissue Repair & Engineering Centre, UCL, Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, Middsex, UK.
Mudera
V
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D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004387:Dupuytren Contracture / Q000378:metabolism* / Q000473:pathology; D025461:Feedback, Physiological / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage*; D015854:Up-Regulation
D053773:Transforming Growth Factor beta1