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    J Hand Surg Br. 2006 Oct;31(5):473-83. Epub 2006 Jul 26.

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

    Source

    Tissue Repair & Engineering Centre, UCL, Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, Middsex, UK.

    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.

    PMID:
    16875762
    [PubMed - indexed for MEDLINE]

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