Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1).
Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1).
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DOI：
10.1038/jidsymp.2009.4
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发表时间：
2009-08
影响因子：
--
通讯作者：
Hearing, Vincent J.
中科院分区：
文献类型：
--
作者：
Yamaguchi, Yuji;Morita, Akimichi;Maeda, Akira;Hearing, Vincent J.
Dickkopf 1（DKK 1）是一种Wnt信号抑制剂，不仅在发育过程中作为头部诱导物发挥作用，而且还调节关节重塑和骨形成，这表明DKK 1在类风湿性关节炎和多发性骨髓瘤的发病机制中发挥作用。我们最近证明，掌跖皮肤成纤维细胞中的DKK 1水平在生理上高于非掌跖皮肤成纤维细胞中观察到的水平。因此，掌跖真皮中富含DKK 1的间充质影响上覆上皮并诱导表皮中的掌跖表型。更具体地，DKK 1通过调节小眼症相关转录因子（MITF）和β-连环蛋白来抑制黑素细胞的功能和生长。此外，DKK 1诱导角质形成细胞中角蛋白9和α-Kelch样ECT 2相互作用蛋白（αKLEIP）的表达，但下调β-catenin、糖原合成酶激酶3β、蛋白激酶C和蛋白酶激活受体2（PAR-2）的表达。用DKK 1处理重建的皮肤通过Wnt/β-连环蛋白信号传导再现了皮肤的色素减退和增厚。这些研究阐明了为什么人类掌跖皮肤比非掌跖皮肤更厚和更白，这是通过影响覆盖表皮的成纤维细胞分泌DKK 1来实现的。因此，DKK 1可用于减少皮肤色素沉着和用于增厚由糖尿病和风湿性皮肤病引起的光老化皮肤和掌跖伤口。
Dickkopf 1 (DKK1), an inhibitor of Wnt signaling, not only functions as a head inducer during development, but also regulates joint remodeling and bone formation, which suggests roles for DKK1 in the pathogenesis of rheumatoid arthritis and multiple myeloma. We recently demonstrated that levels of DKK1 in palmoplantar dermal fibroblasts are physiologically higher than those observed in non-palmoplantar dermal fibroblasts. Thus, the DKK1-rich mesenchyme in palmoplantar dermis affects the overlying epithelium and induces a palmoplantar phenotype in the epidermis. More specifically, DKK1 suppresses melanocyte function and growth via the regulation of microphthalmia-associated transcription factor (MITF) and β-catenin. Furthermore, DKK1 induces the expression of keratin 9 and α-Kelch-like ECT2 interacting protein (αKLEIP) but down-regulates the expression of β-catenin, glycogen synthase kinase 3β, protein kinase C and proteinase-activated receptor-2 (PAR-2) in keratinocytes. Treatment of reconstructed skin with DKK1 reproduces the hypopigmentation and thickening of skin via Wnt/β-catenin signaling. These studies elucidate why human palmoplantar skin is thicker and paler than non-palmoplantar skin via the secretion of DKK1 by fibroblasts that affect the overlying epidermis. Thus, DKK1 may be useful for reducing skin pigmentation and for thickening photo-aged skin and palmoplantar wounds caused by diabetes mellitus and rheumatic skin diseases.
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影响因子：
64.8
作者：
Glinka, A;Wu, W;Niehrs, C
通讯作者：
Niehrs, C
DOI：
10.1083/jcb.200311122
发表时间：
2004-04-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yamaguchi Y;Itami S;Watabe H;Yasumoto K;Abdel-Malek ZA;Kubo T;Rouzaud F;Tanemura A;Yoshikawa K;Hearing VJ
通讯作者：
Hearing VJ
影响因子：
4.8
作者：
Yamaguchi, Yuji;Takahashi, Kaoruko;Hearing, Vincent J.
通讯作者：
Hearing, Vincent J.
DOI：
10.1007/978-1-59259-994-3_6
发表时间：
2006-01-01
期刊：
FROM MELANOCYTES TO MELANOMA: THE PROGRESSION TO MALIGNANCY
影响因子：
--
作者：
Yamaguchi, Yuji;Hearing, Vincent J.
通讯作者：
Hearing, Vincent J.
影响因子：
82.9
作者：
Diarra, Danielle;Stolina, Marina;Schett, Georg
通讯作者：
Schett, Georg