ARTICLE: Alteration to the Skin Barrier Integrity Following Broad-Spectrum UV Exposure in an Ex Vivo Tissue Model

Desmoglein 1) with no effect on Filaggrin. This observation suggests a potential mechanism in which UV penetrates through the stratum corneum to induce apoptosis at the stratum granulosum layer, which in turn reduces the integrity of the adherens junctions. Since adherens junctions provide the mechanical cohesion between the cells in the epidermal layers and the key signaling cues to cytoskeletal dynamics and polarity, the disruption to the adherens junction have significant function implications.²⁸ In skin diseases such as psoriasis vulgaris, Occludin and ZO-1 are up-regulated and Claudins are down-regulated, suggesting that the compromised skin is undergoing active repair.²⁸ The irradiated skin at elevated levels also had increased levels of transglutaminase, which is a hallmark of compromised skin barrier as previously demonstrated in a SLS-challenged skin model.²⁹ The functional implications to the changes to transglutaminase has also been illustrated in patients suffering from atopic dermatitis (AD) and psoriasis, where lesional tissues marked increase in both TGM1 and TGM3.^5,6 The observed similarities in skin barrier changes following UV exposure with patients suffering from skin disorders further illustrates the importance of adequate photoprotection to prevent the alteration of barrier structure after receiving extended sunlight exposure. This is also one of the first works that clearly demonstrates how sunscreen can have direct benefits to the protection from UV-induced barrier damage, as previous studies have focused on the fundamental science of barrier alterations.^14,30

Although this study has revealed very interesting structural and molecular changes the skin goes through as a result of UV irradiation, there are still many unanswered questions in the topic of barrier protection against UV irradiation. This study investigated the effect of balanced physiologically relevant UVA/UVB doses but did not explore whether the contribution of barrier disruption is driven by UVB or UVA wavelengths. One study had demonstrated that while suberythemal doses of UVB can be used as a therapeutic treatment for atopic dermatitis, elevated levels can induce barrier disruption.³¹ This enables our model to be used to evaluate the therapeutic use of UV by monitoring structural and molecular changes within the tissue at varying UVB doses. While we demonstrated the benefit of sunscreen protection, further work is recommended to compare varying sunscreens with and without ceramides. Furthermore, the relationship between the structural disruption with alterations of ceramides and lipids has yet to be clarified and will be addressed in our future work. One of the key unanswered questions is the clinical and consumer relevance of the observed structural disruption and lipid ratio modification as a result of UV irradiation. The following article in this supplement will unpack the potential changes to skin barrier in a clinical study and also illustrate the benefits of a sunscreen and moisturizer routine following sun exposure. We believe through these efforts, the relationship between UV exposure and the alteration of the skin barrier can be explained, therefore illustrating the importance of barrier restoring photoprotection products.

In this study, we have introduced the use of ex vivo skin to identify additional parameters in studying barrier damage following UV exposure. Our results demonstrated that prolonged UV exposure induces epidermal cell death in addition to disruption of key basement membrane proteins. This exposure also altered expression of key differentiation proteins (TGM1, INV) and adherens junction proteins (DSG1, CLD4). Such effects can be ameliorated by the application of a ceramide containing sunscreen.

UV exposure not only induces detrimental effects on skin health and photoaging but has been demonstrated to have acute and prolonged impacts on both the structural and molecular components responsible for maintaining barrier integrity. Further work, which will be an upcoming second part to accompany this study, will be aimed to explore the relationship of the observed results with alterations to the skin ceramide composition following UV exposure. This future study permits for the understanding as to possible alteration of skin ceramide composition following UV exposure and would highlight the importance of introducing proper ceramide blends in sun care and skin care routines to help combat the UV-induced barrier damage and restore skin health following daily sun exposure. Replenishment of essential skin ceramides can not only help to recover the ideal lipid ratio within the skin but to also accelerate recovery of barrier impaired skin. Continued research in the field is needed to not only identify proper lipid combinations that lead to clinical and consumer-perceived benefits following UV exposure, but to also recognize any further benefits of photoprotection associated with UV-induced barrier disruption.

The authors declare no conflict of interest. This research is sponsored by L’Oreal Research & Innovation.

A special thank you to Francoise Bernerd and Dominique Bernard for their scientific advisements, Rajesh Patel for TEM support, and to Yung-Hao Tsou for technical support.

1. Niehues H, Bouwstra JA, El Ghalbzouri A, Brandner JM, Zeeuwen PLJM, van den Bogaard EH. 3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function. Exp Dermatol. 2018;27(5):501-511. doi:10.1111/exd.13531
2. van Smeden J., Janssens M., Gooris G.S. BJA. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta. 2014;1841:295-313.
3. Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):1-15. doi:10.1172/jci. insight.98006