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 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.
| Original language | English |
|---|---|
| Pages (from-to) | 274-283 |
| Number of pages | 10 |
| Journal | Journal of Dermatological Science |
| Volume | 72 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 Dec 1 |
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Keywords
- Melanin
- MITF
- Neural stem cell-conditioned medium
- Tyrosinase
- Wnt inhibitors
ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Molecular Biology
Cite this
Neural stem cells inhibit melanin production by activation of Wnt inhibitors. / Hwang, Insik; Park, Ju Hwang; Park, Hang Soo; Choi, Kyung Ah; Seol, Ki Cheon; Oh, Seung Ick; Kang, Seong Man; Hong, Sunghoi.
In: Journal of Dermatological Science, Vol. 72, No. 3, 01.12.2013, p. 274-283.Research output: Contribution to journal › Article
}
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, Seong Man
AU - Hong, Sunghoi
PY - 2013/12/1
Y1 - 2013/12/1
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 - Melanin
KW - MITF
KW - Neural stem cell-conditioned medium
KW - Tyrosinase
KW - Wnt inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84887159190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887159190&partnerID=8YFLogxK
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 -