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Insulin-Like Growth Factor Binding Protein-6: A Potential Mediator of Myofibroblast Differentiation in Dupuytren’s Disease?

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Dupuytren’s Disease and Related Hyperproliferative Disorders

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Abstract

The expression of IGFBP6 gene and its protein product, insulin-like growth factor binding protein (IGFBP)-6, are down-regulated in Dupuytren’s Disease (DD). As IGFBP-6 is an established negative regulator of IGF-II signaling in other systems, decreased levels of IGFBP-6 may lead to induction of IGF-II-mediated signaling events in Dupuytren’s disease. While the consequences of this signaling are poorly understood, they may include increased myofibroblast differentiation and collagen deposition, both phenotypes of Dupuytren’s Disease. Repression of IGFBP6 gene transcription and protein secretion may be the consequence of increased TGF-β signaling in this disease. IGFBP-6 in combination with TGF-β may have a role in inhibiting contraction of stressed fibroblast populated collagen lattice cultured with DD or patient-matched control cells. Furthermore, we find that addition of IGF-II to these lattices induces contraction. We hypothesize that IGFBP-6 levels may be specifically diminished in Dupuytren’s Disease to allow IGF-II to act in combination with TGF-β to induce the differentiation of fibroblasts to myofibroblasts, and promote collagen deposition. If this proves to be the case, manipulating the levels of IGFBP-6 may inhibit myofibroblast differentiation, collagen deposition and disease progression.

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Authors and Affiliations

  1. Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, St. Joseph’s Health Care, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada

    Christina Raykha & Justin Crawford

  2. Departments of Surgery, Physiology and Pharmacology, Medical Biophysics, Cell and Molecular Biology Laboratory, Hand and Upper Limb Centre, St. Joseph’s Health Care, Lawson Health Research Institute, University of Western Ontario, London, ON, Canada

    Bing Siang Gan & David B. O’Gorman

Authors
  1. Christina Raykha
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  2. Justin Crawford
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  3. Bing Siang Gan
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  4. David B. O’Gorman
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Corresponding author

Correspondence to David B. O’Gorman .

Editor information

Editors and Affiliations

  1. The Hand Center, S Old Dixie Highway 1002, Jupiter, 33458, Florida, USA

    Charles Eaton

  2. Strahlenzentrum Hamburg, Langenhorner Chaussee 369, Hamburg, 22419, Germany

    M. Heinrich Seegenschmiedt

  3. Manchester Interdisciplinary Biocentre, Plastic & Reconstructive Surgery, University of Manchester, Princess Street 131, Manchester, M1 7DN, United Kingdom

    Ardeshir Bayat

  4. Faculty of Medicine, Dept. of Pathology and Immunology, University of Geneva, Rue Michel-Servet 1, Geneva, 1211, Switzerland

    Giulio Gabbiani

  5. Medical Center, Department of Plastic Surgery, University of Groningen, Hanzeplein 1, Groningen, 9713 GZ, Netherlands

    Paul Werker

  6. Dupuytren e.V., Westerbuchberg 60b, Übersee, 83236, Germany

    Wolfgang Wach

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Raykha, C., Crawford, J., Gan, B.S., O’Gorman, D.B. (2012). Insulin-Like Growth Factor Binding Protein-6: A Potential Mediator of Myofibroblast Differentiation in Dupuytren’s Disease?. In: Eaton, C., Seegenschmiedt, M., Bayat, A., Gabbiani, G., Werker, P., Wach, W. (eds) Dupuytren’s Disease and Related Hyperproliferative Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22697-7_20

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  • DOI: https://doi.org/10.1007/978-3-642-22697-7_20

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-22696-0

  • Online ISBN: 978-3-642-22697-7

  • eBook Packages: MedicineMedicine (R0)

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