Extracellular matrix molecules implicated in hypertrophic and keloid scarring

Authors

  • G.P. Sidgwick,

    1. Plastic and Reconstructive Surgery Research, School of Translational Medicine, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
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  • A. Bayat

    Corresponding author
    1. Plastic and Reconstructive Surgery Research, School of Translational Medicine, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    2. Department of Plastic and Reconstructive Surgery, University Hospital of South Manchester (UHSM) NHS Foundation Trust, Wythenshawe Hospital, Wythenshawe, Manchester, UK
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  • Conflicts of interest
    None.

  • Funding source
    The authors would like to thank the Mc George Trust and the NIHR (UK) for their generous support.

A. Bayat. E-mail:ardeshir.bayat@manchester.ac.uk

Abstract

Tissue regeneration repairs the fabric of the skin to maintain homeostasis after injury. The expression and proliferation of extracellular matrix (ECM) molecules in the dermis, mediated by a range of growth factors and cytokines, is a fundamental element of wound repair. Previous work focused on how these complex molecular mechanisms relate to the formation of raised dermal scars, including keloid and hypertrophic scars, characterized by excessive deposition of ECM molecules. However, the mechanisms in the wound repair pathway which lead to the differential expression and organization of ECM molecules observed in different types of scar tissue are not fully understood. To summarize what is known about the expression and composition of ECM molecules in abnormal scarring, an extensive search of the literature was conducted, focusing on keywords connected to skin scarring, hypertrophic scars and keloid disease. The transcription and translation of collagen I and III, fibronectin, laminin, periostin and tenascin are all increased in raised dermal scar tissue. However, hyaluronic acid, dermatopontin and decorin are decreased, and the expression and localisation of fibrillin and elastin fibres in the dermis are altered compared with normal skin and scars. Recent whole genome profiling and proteomic studies have led to the identification of regulatory elements with different expression profiles in hypertrophic and keloid tissue. If the mechanisms of raised dermal scar formation are to be elucidated and effective therapeutic treatments developed, an integrated approach to research is required, focussing on the interactions between ECM molecules, regulatory elements and pathways.

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