Low-Temperature Argon Plasma Regulates Skin Moisturizing and Melanogenesis-Regulating Markers through Yes-Associated Protein.

Hae-Young Kim,Min Jung Lee,Won-Kook Ham,Gaurav Agrahari,Lee-Jung Tak,Tae-Yoon Kim

doi:10.3390/ijms22041895

Hae-Young Kim, Min Jung Lee + Show 4 more

Open Access

https://doi.org/10.3390/ijms22041895

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Abstract

Extensive water loss and melanin hyperproduction can cause various skin disorders. Low-temperature argon plasma (LTAP) has shown the possibility of being used for the treatment of various skin diseases, such as atopic dermatitis and skin cancer. However, the role of LTAP in regulating skin moisturizing and melanogenesis has not been investigated. In this study, we aimed to determine the effect of LTAP on yes-associated protein (YAP), a major transcriptional coactivator in the Hippo signaling pathway that is involved in skin moisturizing and melanogenesis-regulating markers. In normal human epidermal keratinocytes (NHEKs), the human epidermal keratinocyte line HaCaT, and human dermal fibroblasts (HDFs), we found that LTAP exhibited increased expression levels of YAP protein. In addition, the expression levels of filaggrin (FLG), which is involved in natural moisturizing factors (NMFs), and hyaluronic acid synthase (HAS), transglutaminase (TGM), and involucrin (IVL), which regulate skin barrier and moisturizing, were also increased after exposure to LTAP. Furthermore, collagen type I alpha 1 and type III alpha 1 (COL1A1, COL3A1) were increased after LTAP exposure, but the expression level of matrix metalloproteinase-3 (MMP-3) was reduced. Moreover, LTAP was found to suppress alpha-melanocyte stimulating hormone (α-MSH)-induced melanogenesis in murine melanoma B16F10 cells and normal human melanocytes (NHEMs). LTAP regulates melanogenesis of the melanocytes through decreased YAP pathway activation in a melanocortin 1 receptor (MC1R)-dependent manner. Taken together, our data show that LTAP regulates skin moisturizing and melanogenesis through modulation of the YAP pathway, and the effect of LTAP on the expression level of YAP varies from cell to cell. Thus, LTAP might be developed as a treatment method to improve the skin barrier, moisture content, and wrinkle formation, and to reduce melanin generation.

Highlights

The skin protects the body from trauma, regulates body temperature, and balances moisture and electrolytes
We first investigated the effect of Low-temperature argon plasma (LTAP) exposure for 1, 3, or 5 min on the skin barrier and natural moisturizing factors (NMFs) synthesis-related gene expression in HaCaT cells and normal human epidermal keratinocytes (NHEKs)
These results showed that the anti-melanogenesis effect of LTAP is mediated by yes-associated protein (YAP)

Summary

Introduction

The skin protects the body from trauma, regulates body temperature, and balances moisture and electrolytes. Moisture in the skin circulates from the blood to the dermal and epidermal layers, reduces transepidermal water loss, and increases the thickness and density of the skin to prevent aging factors such as pigmentation and wrinkles [1]. Hyaluronic acid (HA) is known to increase moisture content in the skin by regulating hyaluronic acid synthase (HAS)-encoding genes [7]. TGM catalyzes the formation of isopeptide bonds between proteins to prevent water loss, and the main substrates of TGM are epidermal barrier proteins that form protein–lipid matrices such as FLG and IVL. The expression of the genes encoding these proteins increases with the formation of the epidermal barrier [4,5,6]

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