Cutaneous wound healing: recruiting developmental pathways for regeneration
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Cellular and Molecular Life Sciences
REVIEW
Cutaneous wound healing: recruiting developmental pathways for regeneration Kirsten A. Bielefeld • Saeid Amini-Nik Benjamin A. Alman
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Received: 31 January 2012 / Revised: 29 August 2012 / Accepted: 30 August 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/b-catenin, TGF-b, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we
K. A. Bielefeld and S. Amini-Nik are co-first authors. K. A. Bielefeld S. Amini-Nik B. A. Alman (&) Program in Developmental and Stem Cell Biology, Department of Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto Medical Discovery Tower, East Tower, 101 College St., Toronto, ON M5G 1L7, Canada e-mail: [email protected] K. A. Bielefeld e-mail: [email protected] S. Amini-Nik e-mail: [email protected] K. A. Bielefeld B. A. Alman Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada B. A. Alman Department of Surgery, University of Toronto, Toronto, ON M5S 1A8, Canada
outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments. Keywords Wound healing Regeneration Skin Wnt b-Catenin Transforming growth factor b (TGF-b) Notch Hedgehog
Cutaneous wund healing and skin development Cutaneous wound repair recapitulates embryonic skin development in numerous aspects, in an attempt to restore the integrity of the injured tissue. Both processes involve the differentiation, migration, proliferation, and apoptosis of various cell types to create the multilayered tissue that constitutes the skin. Many of the same key signaling pathways that are activated during embryonic skin development are also activated during postnatal cutaneous wound repair; these include the Wnt/b-catenin, Notch, Hedgehog, and various growth factor/cytokine pathways. Furthermore, several ‘embryonic’ extracellular matrix (ECM) components, such as Extra-Domain-A (EDA) fibronectin, are synthesized during postnatal wound repair [1, 2]. Despite these similarities,
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