Neural stem cells inhibit melanin production by activation of Wnt inhibitors

作者：Hwang Insik; Park Ju Hwang; Park Hang Soo; Choi Kyung Ah; Seol Ki Cheon; Oh Seung Ick; Kang Seongman; Hong Sunghoi^*

来源：Journal of Dermatological Science, 2013, 72(3): 274-283.

DOI：10.1016/j.jdermsci.2013.08.006

• Neural stem cell-conditioned medium
• Melanin
• Tyrosinase
• MITF
• Wnt inhibitors

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. %26lt;br%26gt;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). %26lt;br%26gt;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. %26lt;br%26gt;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). %26lt;br%26gt;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.

• 出版日期2013-12