Department of Dermatology, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjyuku, Tokyo, 162-8666, Japan.
Arch Dermatol Res. 2010 May;302(4):283-94. doi: 10.1007/s00403-009-1007-x. Epub 2009 Nov 24.
KIT is an essential receptor that modulates melanocyte function and whose function is disrupted in several pigmentary disorders. However, little is known about the effects of a single UVB exposure on the expression of KIT and two important regulatory transcription factors, MITF and AP-2 alpha, in human melanocytes. We found that a single UVB exposure of human melanocytes induces an early decrease and a subsequent increase in functional KIT expression in concert with up-regulated MITF expression. The increased MITF expression was accompanied by a markedly stimulated and prolonged phosphorylation of p38/CREB. The UVB-stimulated expression of KIT could be completely abolished by a p38 inhibitor, concomitant with a reduced phosphorylation of CREB and a down-regulation of MITF expression. Interestingly, in non-UVB exposed human melanocytes, a MEK inhibitor stimulated the phosphorylation of p38/CREB which was associated with an increased production of MITF and KIT in a pattern similar to that induced by UVB. These findings indicate that UVB stimulates functional KIT expression in human melanocytes via the up-regulation of MITF which is, in turn, due to the activation of p38 and CREB.
KIT 是一种重要的受体，调节黑素细胞的功能，其功能在几种色素沉着紊乱中被破坏。然而，人们对单次 UVB 暴露对人黑素细胞中 KIT 和两个重要调节转录因子 MITF 和 AP-2 alpha 的表达的影响知之甚少。我们发现，单次 UVB 暴露诱导人黑素细胞中功能性 KIT 表达的早期减少和随后增加，同时 MITF 表达上调。增加的 MITF 表达伴随着 p38/CREB 的明显刺激和延长的磷酸化。p38 抑制剂可完全消除 UVB 刺激的 KIT 表达，同时 CREB 的磷酸化减少和 MITF 表达下调。有趣的是，在未暴露于 UVB 的人黑素细胞中，MEK 抑制剂刺激 p38/CREB 的磷酸化，这与 MITF 和 KIT 的产生增加有关，其模式类似于 UVB 诱导的模式。这些发现表明，UVB 通过上调 MITF 刺激人黑素细胞中功能性 KIT 的表达，而 MITF 的上调又归因于 p38 和 CREB 的激活。
