Abstract
Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM) derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF) expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.
Highlights
Melanogenesis is the process of melanin synthesis in melanocytes that determines the color of the skin, hair, and eyes
We found that hUCB-MSC-conditioned media (CM) suppressed α-MSH-induced pigmentation via proteasomal degradation of microphthalmia-associated transcription factor (MITF) via ERK activation in melanocytes
To address the effect of hUCB-MSC-CM on melanogenesis, both Melan-a melanocytes and B16F1 melanoma cells were stimulated with α-MSH, and the cells were further treated with CM derived from bone marrow-MSCs (BM-MSCs), adipocyte-MSCs, human epidermal keratinocytes-MSCs (HEK-MSCs) as well as hUCB-MSCs
Summary
Melanogenesis is the process of melanin synthesis in melanocytes that determines the color of the skin, hair, and eyes. Melanin plays an important role in human skin for cosmetic appearance as well as in the protection of skin from various sources that induce damage such as ultraviolet (UV) irradiation [1]. Many genes involved in pigmentation have been identified. Microphthalmia-associated transcription factor (MITF) is the most critical factor for the regulation of melanogenesis and melanocyte function [2]. PLOS ONE | DOI:10.1371/journal.pone.0128078 May 29, 2015
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