Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G
Kao Biological Science Laboratories, Haga, Tochigi, Japan.
J Invest Dermatol. 2001 Apr;116(4):578-86. doi: 10.1046/j.1523-1747.2001.01290.x.
The interaction of stem cell factor with its receptor, c-kit, is well known to be critical to the survival of melanocytes. Little is known about the role(s) of the stem cell factor/c-kit interaction in epidermal pigmentation, however. To clarify whether the stem cell factor/c-kit signaling has a paracrine role in ultraviolet-B-induced pigmentation, we determined whether the exposure of human keratinocytes, melanocytes, and the epidermis to ultraviolet B light stimulates the expression of stem cell factor or c-kit at the gene and/or protein levels. We further examined whether interrupting the binding of stem cell factor to c-kit by subepidermal injection of a monoclonal antibody to c-kit affects ultraviolet-B-induced pigmentation in brownish guinea pig skin. When human keratinocytes and melanocytes in culture were exposed to ultraviolet B light, transcripts of stem cell factor and c-kit (as assessed by reverse transcription polymerase chain reaction) and expression of those proteins (by enzyme-linked immunosorbent assay and western blotting) increased significantly and peaked at a dose of 20-40 mJ per cm2. In ultraviolet-B-exposed human epidermis, stem cell factor transcripts and protein expression were also markedly enhanced compared with the nonexposed epidermis. Immunohistochemistry with antibodies to stem cell factor revealed an increased staining in the ultraviolet-B-exposed epidermis, which was accompanied by a slight epidermal hyperplasia. In the course of ultraviolet-B-induced pigmentation of brownish guinea pig skin, the subepidermal injection of c-kit inhibitory antibodies completely abolished the induction of pigmentation in the ultraviolet-B-exposed area, and there was no increase in the number of dihydroxyphenylalanine-positive melanocytes. These findings indicate that the stem cell factor/c-kit signaling is critically involved in the biologic mechanism of ultraviolet-B-induced pigmentation.
干细胞因子与其受体c-kit的相互作用对黑素细胞的存活至关重要，这一点已广为人知。然而，关于干细胞因子/c-kit相互作用在表皮色素沉着中的作用却知之甚少。为了阐明干细胞因子/c-kit信号传导在紫外线B诱导的色素沉着中是否具有旁分泌作用，我们确定了人角质形成细胞、黑素细胞和表皮暴露于紫外线B光下是否会在基因和/或蛋白质水平上刺激干细胞因子或c-kit的表达。我们进一步研究了通过皮下注射抗c-kit单克隆抗体阻断干细胞因子与c-kit的结合是否会影响棕色豚鼠皮肤中紫外线B诱导的色素沉着。当培养的人角质形成细胞和黑素细胞暴露于紫外线B光下时，干细胞因子和c-kit的转录本（通过逆转录聚合酶链反应评估）以及这些蛋白质的表达（通过酶联免疫吸附测定和蛋白质印迹法）显著增加，并在剂量为每平方厘米20 - 40 mJ时达到峰值。在暴露于紫外线B的人表皮中，与未暴露的表皮相比，干细胞因子转录本和蛋白质表达也明显增强。用抗干细胞因子抗体进行免疫组织化学显示，暴露于紫外线B的表皮中染色增加，同时伴有轻微的表皮增生。在棕色豚鼠皮肤紫外线B诱导色素沉着的过程中，皮下注射c-kit抑制性抗体完全消除了紫外线B暴露区域色素沉着的诱导，并且二羟基苯丙氨酸阳性黑素细胞的数量没有增加。这些发现表明，干细胞因子/c-kit信号传导在紫外线B诱导色素沉着的生物学机制中起关键作用。
