Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation.
Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation.
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DOI：
10.1083/jcb.200311122
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发表时间：
2004-04-26
期刊：
影响因子：
--
通讯作者：
Hearing VJ
中科院分区：
文献类型：
--
作者：
Yamaguchi Y;Itami S;Watabe H;Yasumoto K;Abdel-Malek ZA;Kubo T;Rouzaud F;Tanemura A;Yoshikawa K;Hearing VJ
我们研究了黑素细胞分化的地形调节是否是通过成纤维细胞衍生因子的间质-上皮相互作用来确定的。人掌跖皮肤中的黑素细胞密度（即，手掌和脚底的皮肤）比非掌跖部位低五倍。与非掌跖成纤维细胞相比，掌跖成纤维细胞显著抑制黑素细胞的生长和色素沉着。使用cDNA微阵列分析，来自掌跖皮肤的成纤维细胞表达高水平的dickkopf 1（DKK 1;经典Wnt信号通路的抑制剂），而nonpalmoplantar成纤维细胞表达更高水平的DKK 3。转染研究表明，DKK 1可能通过β-连环蛋白介导的小眼症相关转录因子活性的调节降低黑素细胞的功能，这反过来又调节黑素细胞的生长和分化。因此，我们的研究结果提供了一个基础来解释为什么手掌和脚底的皮肤与身体的其他区域相比通常是色素减退，并可能解释为什么黑素细胞停止迁移在掌跖区在人类胚胎发育。
We investigated whether or not the topographic regulation of melanocyte differentiation is determined by mesenchymal–epithelial interactions via fibroblast-derived factors. The melanocyte density in palmoplantar human skin (i.e., skin on the palms and the soles) is five times lower than that found in nonpalmoplantar sites. Palmoplantar fibroblasts significantly suppressed the growth and pigmentation of melanocytes compared with nonpalmoplantar fibroblasts. Using cDNA microarray analysis, fibroblasts derived from palmoplantar skin expressed high levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling pathway), whereas nonpalmoplantar fibroblasts expressed higher levels of DKK3. Transfection studies revealed that DKK1 decreased melanocyte function, probably through β-catenin–mediated regulation of microphthalmia-associated transcription factor activity, which in turn modulates the growth and differentiation of melanocytes. Thus, our results provide a basis to explain why skin on the palms and the soles is generally hypopigmented compared with other areas of the body, and might explain why melanocytes stop migrating in the palmoplantar area during human embryogenesis.
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