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Low humidity altered the gene expression profile of keratinocytes in a three-dimensional skin model

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Abstract

Background

The skin is constantly exposed to various external stimuli including humidity variations. Low humidity affects skin properties such as decreased water content of the stratum corneum, reduced skin elasticity, and itching. However, the effects of humidity on the skin cells are not completely understood. This study aimed to investigate how low humidity affects keratinocytes of the skin.

Methods and results

In the present study, the effects of dry environment on the gene expression profile of epidermal keratinocytes were demonstrated using a three-dimensional skin model (3D-skin), composed of keratinocytes. Exposure of 3D-skin to low humidity (relative humidity ~ 10%) increased the expression levels of various genes, including those related to signal transduction and immune system. Accordingly, p38 mitogen-activated protein kinase (MAPK) signaling in keratinocytes of the 3D-skin was activated in response to low humidity for 30 min. Additionally, several chemokines, such as chemokine (C-X-C motif) ligand 1 (CXCL1) and Chemokine (C-C motif) ligand 20 (CCL20), were up regulated after 3 h of exposure to low humidity.

Conclusions

We hypothesize that increased chemokine production may affect the immune system of the whole skin through chemoattractants. Our findings imply that keratinocytes sense low humidity and resultant activation of some cell-signaling pathways leads to variations in gene expression profiles including various chemokines. We provide evidence that keratinocytes adapt to external humidity variations.

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Abbreviations

3D-skin:

Three dimensional skin model

RH:

Relative humidity

TEWL:

Transepidermal water loss

SC:

Stratum corneum

DEGs:

Differentially expressed genes

MAPK:

Mitogen-activated protein kinases

KEGG:

Kyoto Encyclopedia of Genes and Genomes

CXCL1:

Chemokine (C-X-C motif) ligand 1

CXCL3:

Chemokine (C-X-C motif) ligand 3

CXCL8:

Chemokine (C-X-C motif) ligand 8

CXCL10:

Chemokine (C-X-C motif) ligand 10

CCL20:

Chemokine (C-C motif) ligand 20

CCL28:

Chemokine (C-C motif) ligand 28

IL-1:

Interleukin-1

PI3K:

Phosphatidylinositol 3-kinase

TNF:

Tumor necrosis factor

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Acknowledgements

The authors are grateful to Mr. Masakatsu Ota for advice on experimental design. We thank Dr. Tetsuro Iwanaga for useful discussions. The authors would like to thank Ms. Manami Tanaka for technical assistance with the experiments.

Funding

This work was supported by Kracie Home Products, Ltd.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Kenji Shinohara & Mariko Hara-Chikuma

  2. Beauty Care Laboratory, Kracie Home Products, Ltd, 134, Goudo-cho, Hodogaya-ku, Yokohama, Kanagawa, 240-0005, Japan

    Kenji Shinohara

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  1. Kenji Shinohara
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Contributions

KS and MH-C contributed to the study conception and design. KS performed the experiments, and analyzed the data. KS and MH-C wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mariko Hara-Chikuma.

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Shinohara, K., Hara-Chikuma, M. Low humidity altered the gene expression profile of keratinocytes in a three-dimensional skin model. Mol Biol Rep 49, 7465–7474 (2022). https://doi.org/10.1007/s11033-022-07549-0

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