Milk Exosome-Derived MicroRNA-2478 Suppresses Melanogenesis through the Akt-GSK3β Pathway

In-Seon Bae,Sang Hoon Kim

doi:10.3390/cells10112848

Abstract

Exosomes participate in intercellular communication by transferring molecules from donor to recipient cells. Exosomes are found in various body fluids, including blood, urine, cerebrospinal fluid and milk. Milk exosomes contain many endogenous microRNA molecules. MicroRNAs are small noncoding RNAs and have important roles in biological processes. The specific biological functions of milk exosomes are not well understood. In this study, we investigated the effects of milk exosomes on melanin production in melanoma cells and melanocytes. We found that milk exosomes decreased melanin contents, tyrosinase activity and the expression of melanogenesis-related genes in melanoma cells and melanocytes. Bovine-specific miR-2478 in exosomes inhibited melanin production. We found that Rap1a is a direct target gene of miR-2478 in melanoma cells and melanocytes. MiR-2478 overexpression decreased Rap1a expression, which led to downregulated melanin production and expression of melanogenesis-related genes. Inhibition of Rap1a expression decreased melanogenesis through the Akt-GSK3β signal pathway. These results support the role of miR-2478 derived from milk exosomes as a regulator of melanogenesis through direct targeting of Rap1a. These results show that milk exosomes could be useful cosmeceutical ingredients to improve whitening.

Highlights

Cosmeceutical is a compound word combining cosmetic and pharmaceutical, and refers to cosmetics with functional ingredients that have medical effects [1]
The levels of Microphthalmia transcription factor (MITF) and TYR proteins recovered in the cells exposed to milk exosomes after these cells were transfected with the miR-2478 inhibitor (Figure 4D). These results suggested that miR-2478 derived from milk exosomes directly suppressed melanogenesis in mouse melanoma cells
Keratinocytederived soluble factors regulate the melanogenesis of neighboring melanocytes

Summary

Introduction

Cosmeceutical is a compound word combining cosmetic and pharmaceutical, and refers to cosmetics with functional ingredients that have medical effects [1]. Skin was improved through dermatological procedures, but recently, interest in cosmeceuticals has been heightened due to consumers’ desire to obtain these effects through cosmetics. The cosmetic industry has shown an increased interest in recent years in the use of novel cosmeceutical ingredients [2]. Tyrosinase (TYR) is the most important enzyme of melanin synthesis. The melanin synthesis process is induced by TYR activation via MITF, which is an important enzyme involved in the initial stage of the melanin synthesis process, and uses the L-form of tyrosine or DOPA as a substrate to form melanin [5]

Methods

Results

Conclusion