TY - JOUR
T1 - Neural stem cells inhibit melanin production by activation of Wnt inhibitors
AU - Hwang, Insik
AU - Park, Ju Hwang
AU - Park, Hang Soo
AU - Choi, Kyung Ah
AU - Seol, Ki Cheon
AU - Oh, Seung Ick
AU - Kang, Seongman
AU - Hong, Sunghoi
N1 - Funding Information:
This work was supported by grants from Korea University ( K1131492 ), the National Research Foundation of Korea (NRF) ( 20100020349 and 2012M3A9C6050131 ) and the Korea Ministry of Health and Welfare ( A120392 ).
PY - 2013/12
Y1 - 2013/12
N2 - 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 β-catenin in Wnt/β-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 (1.5×104cells/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, MITF, β-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 β-catenin expression in B16 cells and C57/BL-6 mice. NSC-CM negatively regulated Wnt/β-catenin signaling by decreasing the expression of β-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.
AB - 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 β-catenin in Wnt/β-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 (1.5×104cells/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, MITF, β-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 β-catenin expression in B16 cells and C57/BL-6 mice. NSC-CM negatively regulated Wnt/β-catenin signaling by decreasing the expression of β-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.
KW - MITF
KW - Melanin
KW - Neural stem cell-conditioned medium
KW - Tyrosinase
KW - Wnt inhibitors
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U2 - 10.1016/j.jdermsci.2013.08.006
DO - 10.1016/j.jdermsci.2013.08.006
M3 - Article
C2 - 24016750
AN - SCOPUS:84887159190
VL - 72
SP - 274
EP - 283
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 3
ER -