抄録
It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB-induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR-1× HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β-catenin-positive McSCs were increased as compared to non-irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β-catenin, was significantly upregulated in McSCs of UVB-irradiated mice. The Wnt1 expression and the number of nuclear β-catenin-positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte-related genes including Dct in early-passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 652-658 |
| ページ数 | 7 |
| ジャーナル | Experimental Dermatology |
| 巻 | 23 |
| 発行部数 | 9 |
| DOI | |
| 出版物ステータス | Published - 01-01-2014 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Dermatology
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Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae. / Yamada, Takaaki; Hasegawa, Seiji; Inoue, Yu; Date, Yasushi; Arima, Masaru; Yagami, Akiko; Iwata, Yohei; Takahashi, Masayuki; Yamamoto, Naoki; Mizutani, Hiroshi; Nakata, Satoru; Matsunaga, Kayoko; Akamatsu, Hirohiko.
：: Experimental Dermatology, 巻 23, 番号 9, 01.01.2014, p. 652-658.研究成果: Article
TY - JOUR
T1 - Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae
AU - Yamada, Takaaki
AU - Hasegawa, Seiji
AU - Inoue, Yu
AU - Date, Yasushi
AU - Arima, Masaru
AU - Yagami, Akiko
AU - Iwata, Yohei
AU - Takahashi, Masayuki
AU - Yamamoto, Naoki
AU - Mizutani, Hiroshi
AU - Nakata, Satoru
AU - Matsunaga, Kayoko
AU - Akamatsu, Hirohiko
PY - 2014/1/1
Y1 - 2014/1/1
N2 - It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB-induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR-1× HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β-catenin-positive McSCs were increased as compared to non-irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β-catenin, was significantly upregulated in McSCs of UVB-irradiated mice. The Wnt1 expression and the number of nuclear β-catenin-positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte-related genes including Dct in early-passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.
AB - It has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB-induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR-1× HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β-catenin-positive McSCs were increased as compared to non-irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β-catenin, was significantly upregulated in McSCs of UVB-irradiated mice. The Wnt1 expression and the number of nuclear β-catenin-positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte-related genes including Dct in early-passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84913537589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84913537589&partnerID=8YFLogxK
U2 - 10.1111/exd.12496
DO - 10.1111/exd.12496
M3 - Article
C2 - 25040700
AN - SCOPUS:84913537589
VL - 23
SP - 652
EP - 658
JO - Experimental Dermatology
JF - Experimental Dermatology
SN - 0906-6705
IS - 9
ER -