Hasegawa Junichi, Goto Yasufumi, Murata Hiroshi, Takata Minoru, Saida Toshiaki, Imokawa Genji
Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan 2 School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo, Japan.
Pigment Cell Melanoma Res. 2008 Dec;21(6):687-99. doi: 10.1111/j.1755-148x.2008.00492.x.
The hypo-pigmentation of human skin on the palms and the soles compared with other areas of the body has recently been reported to be due to mesenchymal-epithelial interactions via a fibroblast-derived factor, dickkopf 1, an inhibitor of the canonical Wnt signaling pathway. Recently, it has been reported that keratinocytes play a significant role in skin color determination by producing cytokines involved in melanogenesis. Thus, we hypothesized that the downregulated expression of keratinocyte- or fibroblast-derived melanogenic cytokines may also be responsible for the decreased function of palmoplantar (PP) melanocytes in addition to the suppressive effects of dickkopf 1 on melanogenic function in epidermal melanocytes. Immunohistochemistry revealed that the number of tyrosinase, S100alpha, c-KIT, endothelin B receptor (ETBR), SOX10, and microphthalmia-associated transcription factor (MITF) immuno-positive melanocytes is significantly reduced in PP epidermis. In contrast, dopa-histochemistry demonstrated no substantial reduction in melanocyte populations in PP epidermis. Real-time RT-PCR revealed that the expression of stem cell factor (SCF) and endothelin (ET)-1 mRNAs in PP skin was significantly downregulated. In parallel, immunohistochemistry revealed that SCF and ET-1 immuno-staining was markedly attenuated in PP skin. Western blotting revealed that the expression of SCF, c-KIT, and MITF-M proteins was significantly decreased in PP skin. These findings suggest the possibility that downregulation of ET-1/SCF/receptor linkages is also associated with the decreased function of melanocytes in PP skin.
最近有报道称，与身体其他部位相比，人类手掌和脚底皮肤色素减退是由于间充质-上皮相互作用，通过成纤维细胞衍生因子Dickkopf 1实现，Dickkopf 1是经典Wnt信号通路的抑制剂。最近，有报道称角质形成细胞通过产生参与黑色素生成的细胞因子在皮肤颜色决定中发挥重要作用。因此，我们推测角质形成细胞或成纤维细胞衍生的黑色素生成细胞因子表达下调，除了Dickkopf 1对表皮黑素细胞黑色素生成功能的抑制作用外，也可能是掌跖（PP）黑素细胞功能下降的原因。免疫组织化学显示，PP表皮中酪氨酸酶、S100α、c-KIT、内皮素B受体（ETBR）、SOX10和小眼相关转录因子（MITF）免疫阳性黑素细胞的数量显著减少。相比之下，多巴组织化学显示PP表皮中的黑素细胞群体没有实质性减少。实时RT-PCR显示，PP皮肤中干细胞因子（SCF）和内皮素（ET）-1 mRNA的表达显著下调。同时，免疫组织化学显示PP皮肤中SCF和ET-1免疫染色明显减弱。蛋白质印迹显示，PP皮肤中SCF、c-KIT和MITF-M蛋白的表达显著降低。这些发现表明，ET-1/SCF/受体联系的下调也可能与PP皮肤中黑素细胞功能下降有关。
