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Comparison of photodamage in non-pigmented and pigmented human skin equivalents exposed to repeated ultraviolet radiation to investigate the role of melanocytes in skin photoprotection

De Los Santos Gomez, Paola; Costello, Lydia; Goncalves, Kirsty; Przyborski, Stefan

Comparison of photodamage in non-pigmented and pigmented human skin equivalents exposed to repeated ultraviolet radiation to investigate the role of melanocytes in skin photoprotection Thumbnail


Authors

Lydia Costello



Abstract

Introduction: Daily solar ultraviolet (UV) radiation has an important impact on skin health. Understanding the initial events of the UV-induced response is critical to prevent deleterious conditions. However, studies in human volunteers have ethical, technical, and economic implications that make skin equivalents a valuable platform to investigate mechanisms related to UV exposure to the skin. In vitro human skin equivalents can recreate the structure and function of in vivo human skin and represent a valuable tool for academic and industrial applications. Previous studies have utilised non-pigmented full-thickness or pigmented epidermal skin equivalents to investigate skin responses to UV exposure. However, these do not recapitulate the dermal-epidermal crosstalk and the melanocyte role in photoprotection that occurs in vivo. In addition, the UV radiation used in these studies is generally not physiologically representative of real-world UV exposure. Methods: Well-characterised pigmented and non-pigmented skin equivalents that contain human dermal fibroblasts, endogenous secreted extracellular matrix proteins (ECM) and a well-differentiated and stratified epidermis have been developed. These constructs were exposed to UV radiation for ×5 consecutive days with a physiologically relevant UV dose and subsequently analysed using appropriate end-points to ascertain photodamage to the skin. Results: We have described that repeated irradiation of full-thickness human skin equivalents in a controlled laboratory environment can recreate UV-associated responses in vitro, mirroring those found in photoexposed native human skin: morphological damage, tanning, alterations in epidermal apoptosis, DNA lesions, proliferation, inflammatory response, and ECM-remodelling. Discussion: We have found a differential response when using the same UV doses in non-pigmented and pigmented full-thickness skin equivalents, emphasising the role of melanocytes in photoprotection.

Citation

De Los Santos Gomez, P., Costello, L., Goncalves, K., & Przyborski, S. (2024). Comparison of photodamage in non-pigmented and pigmented human skin equivalents exposed to repeated ultraviolet radiation to investigate the role of melanocytes in skin photoprotection. Frontiers in Medicine, 11, Article 1355799. https://doi.org/10.3389/fmed.2024.1355799

Journal Article Type Article
Acceptance Date Mar 20, 2024
Online Publication Date Apr 18, 2024
Publication Date Apr 18, 2024
Deposit Date Apr 18, 2024
Publicly Available Date Apr 19, 2024
Journal Frontiers in Medicine
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 11
Article Number 1355799
DOI https://doi.org/10.3389/fmed.2024.1355799
Keywords photodamage, UV radiation, human skin equivalents, photoprotection, pigmentation, melanocytes
Public URL https://durham-repository.worktribe.com/output/2388218

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