■每日太阳紫外线(UV)辐射对皮肤健康有重要影响。了解UV诱导的响应的初始事件对于防止有害条件至关重要。然而,对人类志愿者的研究具有伦理意义,技术,和经济意义,使皮肤等效物成为一个有价值的平台,以研究与紫外线暴露于皮肤有关的机制。体外人皮肤等同物可以重建体内人皮肤的结构和功能,并且代表了用于学术和工业应用的有价值的工具。先前的研究已经利用非色素沉着的全厚度或色素沉着的表皮皮肤等同物来研究皮肤对UV暴露的反应。然而,这些并没有概括体内发生的真皮-表皮串扰和黑素细胞在光保护中的作用。此外,这些研究中使用的UV辐射通常不是现实世界UV暴露的生理代表。
■含有人类真皮成纤维细胞的特征明确的色素和非色素皮肤等效物,已经开发了内源性分泌的细胞外基质蛋白(ECM)和分化良好的分层表皮。将这些构建体以生理相关的UV剂量连续5天暴露于UV辐射,随后使用适当的终点进行分析以确定对皮肤的光损伤。
■我们已经描述了在受控的实验室环境中重复照射全厚度人类皮肤等效物可以在体外重建与紫外线相关的反应,反映了在曝光的天然人体皮肤中发现的那些:形态损伤,晒黑,表皮细胞凋亡的改变,DNA损伤,扩散,炎症反应,和ECM重塑。
■我们发现,当在非色素和色素全层皮肤等效物中使用相同的紫外线剂量时,会产生不同的反应,强调黑素细胞在光保护中的作用。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.