Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and enclothelin-1, in ultraviolet B-induced human melanogenesis
Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and enclothelin-1, in ultraviolet B-induced human melanogenesis
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DOI：
10.1016/s0002-9440(10)63260-9
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发表时间：
2004-12-01
影响因子：
6
通讯作者：
Imokawa, G
中科院分区：
文献类型：
--
作者：
Hachiya, A;Kobayashi, A;Imokawa, G
干细胞因子（SCF）和内皮素-1（ET-1）在紫外线B（UVB）照射后在蛋白和基因水平上表达上调，在UVB诱导的色素沉着中起重要作用。然而，很少有人知道SCF和ET-1在UVB暴露的人表皮表达的时间顺序和协调作用，在表皮色素沉着。为了澄清这样的参数在UVB暴露的人皮肤，我们测量了SCF和ET-1（以及其相应的受体）在基因水平上的表达模式在UVB诱导的人类色素沉着的不同时间。当人前臂皮肤暴露于两个最小剂量的UVB辐射时，SCF mRNA转录本的表达在辐射后3天显著增强，SCIF受体（c-KIT）mRNA转录本的表达在早期降低，随后恒定。与此相反，ET-1和内皮素B受体（ETBR）mRNA表达的上调同步在5至10天后，与酪氨酸酶mRNA转录本的表达增加和色素沉着的增加。与此同时，酪氨酸酶和ETBR蛋白以及ET-1的表达在照射后7至10天上调，而KIT蛋白在照射后3天下降，并在照射后5天恢复到未照射的对照水平。当用人重组SCF处理培养的人黑素细胞时，ETBR蛋白表达和I-125标记的ET-1与ETBR的结合显著增加，进一步表明SCF在UVB诱导的黑素生成中的早期表达的优先和协调作用。这些发现表明，SCF/KIT信号主要参与UVB诱导的人类色素沉着的早期阶段，在此期间，它刺激与UVB诱导的黑素生成的后期阶段相关的ET-1/ETB 1 R连接。
Stem cell factor (SCF) and endothelin-1 (ET-1) have been reported to be up-regulated at the protein and gene levels in human epidermis after ultraviolet B (UVB) irradiation and to play central roles in UVB-induced pigmentation. However, little is known about the time sequence of SCF and ET-1 expression in UVB-exposed human epidermis and the coordination of their roles during epidermal pigmentation. To clarify such parameters in UVB-exposed human skin, we measured the expression patterns of SCF and ET-1 (as well as of their corresponding receptors) at the gene level at various times during UVB-induced human pigmentation. When human forearm skin was exposed to UVB radiation at two minimal erythemal doses, the expression of SCF mRNA transcripts was significantly enhanced at 3 days after irradiation with an early decrease and subsequently constant expression of SCIF receptor (c-KIT) mRNA transcripts. In contrast, up-regulation of ET-1 and endothelin B receptor (ETBR) mRNA expression was synchronized at 5 to 10 days after irradiation in concert with an increased expression of tyrosinase mRNA transcripts and the increase in pigmentation. In parallel the expression of tyrosinase and ETBR proteins as well as ET-1 was up-regulated at 7 to 10 days after irradiation, whereas KIT protein decreased at 3 days after irradiation and returned to the nonirradiated control level at 5 days after irradiation. When cultured human melanocytes were treated with human recombinant SCF, ETBR protein expression and the binding of I-125-labeled ET-1 to the ETBR were significantly increased, further suggesting the preferential and coordinated role of early expression of SCF in UVB-induced melanogenesis. These findings suggest that SCF/KIT signaling is predominantly involved in the early phase of UVB-induced human pigmentation during which it stimulates the ET-1/ETB,,R linkage that is associated with the later phase of UVB-induced melanogenesis.