Neural stem cells inhibit melanin production by activation of Wnt inhibitors
- Authors
- Hwang, Insik; Park, Ju-Hwang; Park, Hang-Soo; Choi, Kyung-Ah; Seol, Ki-Cheon; Oh, Seung-Ick; Kang, Seongman; Hong, Sunghoi
- Issue Date
- Dec-2013
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- Neural stem cell-conditioned medium; Melanin; Tyrosinase; MITF; Wnt inhibitors
- Citation
- JOURNAL OF DERMATOLOGICAL SCIENCE, v.72, no.3, pp.274 - 283
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DERMATOLOGICAL SCIENCE
- Volume
- 72
- Number
- 3
- Start Page
- 274
- End Page
- 283
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101530
- DOI
- 10.1016/j.jdermsci.2013.08.006
- ISSN
- 0923-1811
- Abstract
- Background: Melanin for skin pigmentation is synthesized from tyrosine via an enzymatic cascade that is controlled by tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase/tyrosinase related protein 2 (Dct/TRP2), which are the targets of microphthalmia-associated transcription factor (MITF). MITF is a master regulator of pigmentation and a target of beta-catenin in Wnt/beta-catenin signaling during melanocyte differentiation. Stem cells have been used in skin pigmentation studies, but the mechanisms were not determined for the conditioned medium (CM)-mediated effects. Objectives: In this study, the inhibition and mechanisms of melanin synthesis were elucidated in B16 melanoma cells and UV-B irradiated C57/BL-6 mice that were treated with human neural stem cell-conditioned medium (NSC-CM). Methods: B16-F10 melanoma cells (1.5 x 10(4) cells/well) and the shaved dorsal skin of mice were pretreated with various amount (5, 10, 20, 50, and 100%) of NSC-CM. Melanin contents and TYR activity were measured by a Spectramax spectrophotometer. The expression of TYR, TRP1, Dct/TRP2, MITE, beta-catenin and Wnt inhibitors were evaluated by RT-PCR and western blot. The dorsal skin samples were analyzed by immunofluorescence with various antibodies and compared with that control of tissues. Results: Marked decreases were evident in melanin content and TYR, TRP1, DCT/TRP2, MITF, and beta-catenin expression in B16 cells and C57/BL-6 mice. NSC-CM negatively regulated Wnt/beta-catenin signaling by decreasing the expression of beta-catenin protein, which resulted from robust expression of Wnt inhibitors Dickkopf-1 (DKK1) and secreted frizzled-related protein 2 (sFRP2). Conclusions: These results demonstrate that NSC-CM suppresses melanin production in vitro and in vivo, suggesting that factors in NSC-CM may play an important role in deregulation of epidermal melanogenesis. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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