In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin

Marrot, Laurent; Planel, Emilie; Ginestet, Anne-Claire; Belaïdi, Jean-Philippe; Jones, Christophe; Meunier, Jean‐Roch

doi:10.1039/b9pp00145j

Cited by 16 publications

(13 citation statements)

References 52 publications

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“…Regarding the role of p53 in DNA repair, increased p53 expression correlates with increased DNA damage, suggesting that the loss of Nrf2 may fail to protect DNA but could enable abundant p53 to repair the DNA damage. Indeed, a previous study showed that the extent of DNA damage correlates with the amount of UV exposure in various skin cells and models [34]. In our study, the higher p53 expression observed in Nrf2 KO mice after UVB exposure could be an indicator of more sustained DNA damage in need of repair.…”

Section: Discussionsupporting

confidence: 58%

Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages

et al. 2014

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Nrf2 plays a critical role in defending against oxidative stress and inflammation. We previously reported that Nrf2 confers protection against ultraviolet-B (UVB)-induced inflammation, sunburn reaction, and is involved in sulforaphane-mediated photo-protective effects in the skin. In this study, we aimed to demonstrate the protective role of Nrf2 against inflammation-mediated extracellular matrix (ECM) damage induced by UVB irradiation. Ear biopsy weights were significantly increased in both Nrf2 wild-type (Nrf2 WT) and knockout (Nrf2 KO) mice one week after UVB irradiation. However, these weights increased more significantly in KO mice compared to WT mice, suggesting a greater inflammatory response in KO mice. In addition, we analyzed the protein expression of numerous markers, including macrophage inflammatory protein-2 (MIP-2), pro-matrix metalloproteinase-9 (MMP-9), and p53. p53, a regulator of DNA repair, was overexpressed in Nrf2 KO mice, indicating that the absence of Nrf2 led to more sustained DNA damage. There was also more substantial ECM degradation and increased inflammation in UVB-irradiated Nrf2 KO mice compared to UVB-irradiated WT mice. Furthermore, the protective effects of Nrf2 in response to UVB irradiation were mediated by increased HO-1 protein expression. Collectively, our results show that Nrf2 plays a key role in protecting against UVB irradiation and that the photo-protective effect of Nrf2 is closely related to the inhibition of ECM degradation and inflammation.

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Section: Discussionsupporting

confidence: 58%

Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages

et al. 2014

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“…After exposing the skin model to DUVR 13 J cm −2 , we examined the modulation of 43 genes involved in different UV‐induced signalling pathways in dermal fibroblasts and epidermal keratinocytes respectively. Genes were considered to be modulated by DUVR when MF was ≥2 or ≤0.5 with a significant P < 0.05 .…”

Section: Resultsmentioning

confidence: 99%

Validation of a predictive method for sunscreen formula evaluation using gene expression analysis in a Chinese reconstructed full‐thickness skin model

Liu

Wang

Xie

et al. 2019

Intern J of Cosmetic Sci

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Objective This study aimed to establish a predictive in vitro method for assessing the photoprotective properties of sunscreens using a reconstructed full‐thickness skin model. Materials and Methods A full‐thickness skin model reconstructed with human fibroblasts and keratinocytes isolated from Chinese skin was exposed to daily UV radiation (DUVR). We examined the transcriptomic response, identifying genes for which expression was modulated by DUVR in a dose‐dependent manner. We then validated the methodology for efficacy evaluation of different sunscreens formulas. Results The reconstructed skin model was histologically consistent with human skin, and upon DUVR exposure, the constituent fibroblasts and keratinocytes exhibited transcriptomic alterations in pathways associated with oxidative stress, inflammation and extracellular matrix remodelling. When used to evaluate sunscreen protection on the model, the observed level of protection from UV‐induced gene expression was consistent with the corresponding protection factors determined clinically and allowed for statistical ranking of sunscreen efficacy. Conclusions Within this study we show that quantification of gene modulation within the reconstructed skin model is a biologically relevant approach with sensitivity and predictability to evaluate photoprotection products.

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“…The CPD detection assay is an important tool for evaluating genotoxicity in epithelial cells, as these lesions are highly mutagenic and typically induced by UVB radiation (Marrot et al, 2010). After 1 hour of treatment, there is an increase in the amount of CPDs in the carbaryl and solar radiation combined treatment group and, after 6 hours of treatment, there is an equal response between the combined treatment group and the solar radiation group (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes

Ferrucio

Tiago

Fannin

et al. 2017

Toxicology in Vitro

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Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, the main etiologic factor for skin carcinogenesis. We hypothesized that carbaryl exposure may increase deleterious effects of UV solar radiation on skin melanocytes. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100 μM) and solar radiation (375 mJ/cm2). In a microarray analysis, carbaryl, but not solar radiation, induced an oxidative stress response, evidenced by the upregulation of antioxidant genes, such as Hemeoxygenase-1 (HMOX1), and downregulation of Microphtalmia-associated Transcription Factor (MITF), the main regulator of melanocytic activity; results were confirmed by qRT-PCR. Carbaryl and solar radiation induced a gene response suggestive of DNA damage and cell cycle alteration. The expression of CDKN1A, BRCA1/2 and MDM2 genes was notably more intense in the combined treatment group, in a synergistic manner. Flow cytometry assays demonstrated S-phase cell cycle arrest, reduced apoptosis levels and faster induction of cyclobutane pyrimidine dimers (CPD) lesions in carbaryl treated groups. Our data suggests that carbaryl is genotoxic to human melanocytes, especially when associated with solar radiation.

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In vitro tools for photobiological testing: molecular responses to simulated solar UV of keratinocytes growing as monolayers or as part of reconstructed skin

Cited by 16 publications

References 52 publications

Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages

Nrf2 null enhances UVB-induced skin inflammation and extracellular matrix damages

Validation of a predictive method for sunscreen formula evaluation using gene expression analysis in a Chinese reconstructed full‐thickness skin model

Molecular effects of 1-naphthyl-methylcarbamate and solar radiation exposures on human melanocytes

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