Abstract

Dermal macrophages containing melanin increase skin pigmentation since dermal melanin removal is slower than epidermal melanin removal. Lymphatic vessels are also involved in melanin clearance. We evaluated whether radiofrequency (RF) irradiation induced an increase in HSP90, which promotes lymphangiogenesis by activating the BRAF/MEK/ERK pathway and decreasing tyrosinase activity, in the UV-B exposed animal model. The HSP90/BRAF/MEK/ERK pathway was upregulated by RF. Tyrosinase activity and the VEGF-C/VEGFR 3/PI3K/pAKT1/2/pERK1/2 pathway, which increase lymphangiogenesis, as well as the expression of the lymphatic endothelial marker LYVE-1, were increased by RF. Additionally, the number of melanin-containing dermal macrophages, the melanin content in the lymph nodes, and melanin deposition in the skin were decreased by RF. In conclusion, RF increased HSP90/BRAF/MEK/ERK expression, which decreased tyrosinase activity and increased lymphangiogenesis to eventually promote the clearance of dermal melanin-containing macrophages, thereby decreasing skin pigmentation.

Highlights

  • Skin hyperpigmentation is usually accompanied by post-inflammatory hyperpigmentation or melasma [1]

  • We evaluated whether RF irradiation increases HSP90 production, which sequentially leads to increased BRAF/mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) activity in the UV-B induced hyperpigmentation animal model in this study

  • We evaluated whether RF affects the expression of Hsp90, Braf, Mek, and Erk in UV-B exposed animal skin

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Summary

Introduction

Skin hyperpigmentation is usually accompanied by post-inflammatory hyperpigmentation or melasma [1]. Macrophages containing melanin travel to the epidermis, where macrophages further phagocytose melanosomes and return to the dermis [2,3] Through these processes, increased melanin deposition leads to hyperpigmentation [7]. Melanophages are frequently exhibited in the lymph nodes of patients with dermal pigmentation induced by inflammatory skin diseases [9,10] Based on these results, melanin in the dermis might be transported through the lymphatic system. HSP90 upregulates protein kinase B (AKT) or extracellular signal-regulated kinase (ERK), which increases cell migration during wound healing or cancer metastasis [33]. We evaluated whether RF irradiation increases HSP90 production, which sequentially leads to increased BRAF/MEK/ERK activity in the UV-B induced hyperpigmentation animal model in this study. Enhanced lymphangiogenesis through tyrosinase inhibition leads to increased clearance of dermal melanophages and decreased skin pigmentation, especially in the dermis

Results
Discussion
In Vitro Model and RF Irradiation
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