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Overexpression of manganese superoxide dismutase in human dermal fibroblasts enhances the contraction of free floating collagen lattice: implications for ageing and hyperplastic scar formation

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Abstract

Cell–matrix interactions are of significant importance for tissue homeostasis of the skin and, if disturbed, may lead to ageing and hyperplastic scar formation. We have studied fibroblasts stably overexpressing manganese superoxide dismutase (MnSOD) with a defined capacity for the removal of superoxide anions and concomitant accumulation of hydrogen peroxide to evaluate the role of enhanced MnSOD activity on the dynamics of cell–matrix interactions in the three-dimensional collagen lattice contraction assay. MnSOD overexpressing fibroblast populated collagen lattices revealed a significantly enhanced contraction compared to collagen lattices populated with vector control cells. The enhanced collagen lattice contraction was in part due to an increase in active TGF-β1 and the accumulation of H2O2 in MnSOD overexpressing fibroblasts populated collagen lattices. Inhibition of TGF-β1 signalling by the ALK4,5,7 kinases’ inhibitor SB431542 at least partly inhibited the enhanced collagen lattice contraction of MnSOD overexpressing fibroblasts populated lattices. In addition, supplementation of vector control fibroblast populated collagen lattices with recombinant TGF-β1 concentration dependently enhanced the collagen lattice contraction. In the presence of the antioxidant Ebselen, a mimic of H2O2 and other hydroperoxides/peroxynitrite-detoxifying glutathione peroxidase, collagen lattice contraction and the activation of TGF-β1 were significantly reduced in collagen lattices populated with MnSOD overexpressing fibroblasts. Collectively, these data suggest that H2O2 or other hydroperoxides or peroxynitrite or a combination thereof may function as important second messengers in collagen lattice contraction and act at least in part via TGF-β1 activation.

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Acknowledgments

We are grateful to the German Research Foundation (DFG) to financially support the Clinical Research Group KFO 142 “Molecular and Cellular Ageing—From Mechanisms to Clinical Perspectives”, with a project assigned to K-SK. We thank the European Union to support us in the Proteomage and Cascade Programme. We are indebted to Mrs. Hannelore Cox for professional editing of the manuscript.

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Authors and Affiliations

  1. Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081, Ulm, Germany

    Nicolai Treiber, Thorsten Peters, Anca Sindrilaru, Roman Huber, Matthias Kohn, Abhijit Basu, Pallab Maity, Mandy Koller, Sebastian Iben, Meinhard Wlaschek & Karin Scharffetter-Kochanek

  2. Department of Internal Medicine I, University of Ulm, Ulm, Germany

    André Menke

  3. Institute of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany

    Karlis Briviba

  4. Division of Gene Therapy, University of Ulm, Ulm, Germany

    Florian Kreppel & Stefan Kochanek

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Treiber, N., Peters, T., Sindrilaru, A. et al. Overexpression of manganese superoxide dismutase in human dermal fibroblasts enhances the contraction of free floating collagen lattice: implications for ageing and hyperplastic scar formation. Arch Dermatol Res 301, 273–287 (2009). https://doi.org/10.1007/s00403-009-0935-9

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