Temporal transcriptomic analysis of human primary keratinocytes exposed to β-naphthoflavone highlights the protective efficacy of skin to environmental pollutants

Quantin, Paul; Patatian, Angela; Floreani, Maxime; Egles, Christophe; Benech, Philippe; Ficheux, H.

doi:10.1016/j.tiv.2020.104822

Cited by 2 publications

(1 citation statement)

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“…This mitochondrial alteration is responsible for changes in other processes such as lipid peroxidation, decreased collagen biosynthesis and increased collagen degradation via the induction of metalloproteinases. In line with reported observations, 42,43 the induction of several NRF2 target genes (HMOX1, AKR1C1, AKR1C3, PRDX1, SLC7A11, SRXN1, TXNRD1) was detected in HSE exposed to CS. Among them, NRF2 and AKR1C3 protein expressions were also confirmed by immunostaining (Figure 4).…”

Section: F I G U R Esupporting

confidence: 92%

Impact of cigarette smoke on physical‐chemical and molecular proprieties of human skin in an ex vivo model

Percoco

Patatian

Eudier

et al. 2020

Experimental Dermatology

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Background: This is a study about the skin ageing exposome, focusing on the effect of cigarette smoke. Human living skin explants (HSE) were exposed to cigarette smoke (CS) of two cigarettes for 2 hours using a custom-made exposure chamber, the Pollubox ® . Effects on the surface physico-chemistry and molecular properties of the skin were analyzed and reported for the first time.Basic Procedures: To this end, transcriptomic study followed by immunohistochemistry, MDA (Malondialdehyde Dosage), and surface physio-chemistry data: surface free energy determination, TEWL (Trans Epidermal Water Loss), skin pH and FT-IR (Fourier Transform-Infrared) spectroscopy of the explant were collected from untreated and treated HSE.Main Findings: Results showed a decrease of the total surface free energy of the treated HSE. This decrease reflected higher interactions with polar compounds from the environment and consequently a decrease of the surface hydrophobicity.Additionally, an increase of TEWL and skin pH was observed after treatment.The transcriptomic analysis showed downregulation of mitochondrial genes (PON2-NDUFA4L2-ATP1A1-ALDH2-PRODH) combined with an increase of MDA in CStreated HSE.Conclusions: CS-induced oxidation of lipids at HSE surface alters the skin barrier: interactions with polar products are enhanced and the lipid chain packing at the surface is modified. Consequently, skin permeability could increase which correlated with repression of CA9 and AQP1 genes. Beside activation of AHR-NRF2 pathway in CS-exposed HSE, our results suggested that mitochondrial functions were strongly impacted and oxidized lipids failed to be eliminated promoting skin barrier alteration.A mitophagy activity was suggested through the confirmation of PINK1 accumulation in the epidermis by immunostaining.

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Section: F I G U R Esupporting

confidence: 92%

Impact of cigarette smoke on physical‐chemical and molecular proprieties of human skin in an ex vivo model

Percoco

Patatian

Eudier

et al. 2020

Experimental Dermatology

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Dermatokinetics: Advances and Experimental Models, Focus on Skin Metabolism

Quantin

Stricher

Catoire³

et al. 2022

CDM

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Numerous dermal contact products, such as drugs or cosmetics, are applied on the skin, the first protective barrier to their entrance into the organism. These products contain various xenobiotic molecules that can penetrate the viable epidermis. Many studies have shown that keratinocyte metabolism could affect their behavior by biotransformation. While aiming for detoxification, toxic metabolites can be produced. These metabolites may react with biological macromolecules often leading to sensitization reactions. After passing through the epidermis, xenobiotics can reach the vascularized dermis and therefore be bioavailable and distributed into the entire organism. To highlight these mechanisms, dermatokinetics, based on the concept of pharmacokinetics, has been developed recently. It provides information on the action of xenobiotics that penetrate the organism through the dermal route. The purpose of this review is first to describe and synthesize the dermatokinetics mechanisms to consider when assessing the absorption of a xenobiotic through the skin. We focus on skin absorption and specifically on skin metabolism, the two main processes involved in dermatokinetics. In addition, experimental models and methods to assess dermatokinetics are described and discussed to select the most relevant method when evaluating, in a specific context, dermatokinetics parameters of a xenobiotic. We also discuss the limits of this approach as it is notably used for risk assessment in the industry where scenario studies generally focus only on one xenobiotic and do not consider interactions with the rest of the exposome. The hypothesis of adverse effects due to the combination of chemical substances in contact with individuals and not to a single molecule are being increasingly studied and embraced in the scientific community.

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Temporal transcriptomic analysis of human primary keratinocytes exposed to β-naphthoflavone highlights the protective efficacy of skin to environmental pollutants

Cited by 2 publications

References 40 publications

Impact of cigarette smoke on physical‐chemical and molecular proprieties of human skin in an ex vivo model

Impact of cigarette smoke on physical‐chemical and molecular proprieties of human skin in an ex vivo model

Dermatokinetics: Advances and Experimental Models, Focus on Skin Metabolism

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