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Purinoceptor expression on keratinocytes reflects their function on the epidermis during chronic venous insufficiency

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Abstract

Purines are extracellular nucleotides that have long-term effects on keratinocyte proliferation, differentiation and death through P2Y1, P2Y2, P2X5 and P2X7 receptors. This study examined changes in expression of these P2 receptors on lower leg epidermal keratinocytes in control and chronic venous insufficiency (CVI) states. Lower limb skin biopsies from CVI (CEAP classification 4a and 4b) and control skin were immunostained for the above P2 receptor subtypes and epidermal area was calculated. Our results with CVI show an increase in P2Y1 and P2Y2 receptor expression in basal and spinosal layers of the epidermis and an increase of P2X5 receptors mainly in the spinosal layer and extending further into the stratum granulosum. In contrast, P2X7 receptors were reduced in the stratum corneum in CVI. In conclusion, a thinner epidermis was found in CVI, which might be the result of the changes in expression of P2Y and P2X receptors on keratinocytes: that is, increased proliferation via P2Y1 and P2Y2 receptors and reduced P2X7 receptor-mediated cell death opposed by a dominant decrease in cell numbers as a result of increased P2X5 receptor-mediated differentiation (which is in effect antiproliferative). Thus, increased keratinocyte P2X5 receptor activity may, in part, be accountable for epidermal thinning in CVI.

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Acknowledgments

We would like to thank the vascular surgeons at the Royal Free Hospital, Pond St, London and the cardiothoracic surgeons at the Heart Hospital, Westmoreland St, London, for their careful excision of the skin biopsies.

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Authors and Affiliations

  1. Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF, UK

    Matthew J. Metcalfe & Geoffrey Burnstock

  2. Department of Vascular Surgery, Royal Free Hospital, Pond Street, London, NW3 2QG, UK

    Daryll M. Baker

Authors
  1. Matthew J. Metcalfe
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  2. Daryll M. Baker
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  3. Geoffrey Burnstock
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Correspondence to Geoffrey Burnstock.

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Metcalfe, M.J., Baker, D.M. & Burnstock, G. Purinoceptor expression on keratinocytes reflects their function on the epidermis during chronic venous insufficiency. Arch Dermatol Res 298, 301–307 (2006). https://doi.org/10.1007/s00403-006-0693-x

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  • DOI: https://doi.org/10.1007/s00403-006-0693-x

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