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Identification of biomarkers involved in differential profiling of hypertrophic and keloid scars versus normal skin

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Abstract

Among raised dermal scar types, keloid (KS) and hypertrophic scars (HS) are considered to present clinical similarities, but there are no known specific biomarkers that allow both scar types to be easily distinguished. Development and progression of raised dermal scars comprises the activation of several molecular pathways and cell defence mechanisms leading to elevated extracellular matrix component synthesis, delayed apoptosis, altered migration and differentiation. Therefore, the aim here was to identify biomarkers that may differentiate between KS and HS compared to normal skin (NS). To achieve this aim, NS (n = 14), KS (n = 14) and HS (n = 14) biopsies were evaluated using histology by H&E staining. Tissue biopsies and primary fibroblasts (passages 0–4) were employed to assess the gene expression levels of 21 biomarkers selected from our previous microarray studies using qRT-PCR. Finally, protein expression was evaluated using In-Cell Western Blotting in primary fibroblasts (p 0–4). Our results demonstrated that out of the 21 biomarkers screened at mRNA and protein levels, α2β1-integrin, Hsp27, PAI-2, MMP-19 and CGRP showed significantly higher expression (p < 0.05) in KS compared to NS and HS. Additionally, these five key biomarkers were found to be significantly higher (p < 0.05) at mRNA level in KS taken from the sternum, a region known to be subjected to high mechanical forces in the body during the performance of daily movements. In conclusion, our findings offer potential molecular targets in raised dermal scars differentiation. Future targeted research may allow provision of diagnostic and prognostic markers in keloid versus hypertrophic scars.

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Authors and Affiliations

  1. Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology (MIB), University of Manchester, 131 Princess Road, Manchester, M1 7ND, UK

    Edna Suarez, Farhatullah Syed & Ardeshir Bayat

  2. The Bioengineering Group, School of Materials, University of Manchester, Manchester, UK

    Edna Suarez, Teresa Alonso-Rasgado & Ardeshir Bayat

  3. Faculty of Medical and Human Sciences, Institute of Inflammation and Repair, University Hospital of South Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK

    Farhatullah Syed & Ardeshir Bayat

  4. Centre for Dermatology, University of Manchester, Manchester, M13 9PT, UK

    Ardeshir Bayat

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  1. Edna Suarez
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  2. Farhatullah Syed
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  3. Teresa Alonso-Rasgado
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Suarez, E., Syed, F., Alonso-Rasgado, T. et al. Identification of biomarkers involved in differential profiling of hypertrophic and keloid scars versus normal skin. Arch Dermatol Res 307, 115–133 (2015). https://doi.org/10.1007/s00403-014-1512-4

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  • DOI: https://doi.org/10.1007/s00403-014-1512-4

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