Transforming growth factor-β1 decreases melanin synthesis via delayed extracellular signal-regulated kinase activation
Transforming growth factor-β1 decreases melanin synthesis via delayed extracellular signal-regulated kinase activation
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DOI：
10.1016/j.biocel.2003.10.023
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发表时间：
2004-08-01
影响因子：
4
通讯作者：
Park, KC
中科院分区：
文献类型：
--
作者：
Kim, DS;Park, SH;Park, KC
转化生长因子-β 1（TGF-β 1）在细胞增殖、分化和凋亡中起关键作用。在这项研究中，我们研究了TGF-β 1对黑素生成的影响，使用自发永生化的小鼠黑素细胞系，Mel-Ab。我们的研究结果表明，TGF-β 1显着抑制黑色素合成的浓度依赖性的方式，它降低了酪氨酸酶的活性，限速黑色素生成酶。我们还发现TGF-β 1降低了小眼症相关转录因子（MITF）启动子活性，并降低了MITF、酪氨酸酶、酪氨酸酶相关蛋白-1（TRP-1）和TRP-2蛋白的产生。此外，发现TGF-β 1诱导细胞外信号调节激酶（ERK）激活延迟6小时，而许多生长因子激活ERK在几分钟内短暂。此外，特异性ERK通路抑制剂PD 98059阻断了TGF-β 1诱导的色素减退效应。还发现PD 98059消除TGF-β 1介导的MITF、酪氨酸酶、TRP-1和TRP-2产生的下调。这些结果表明，ERK途径可能参与黑素生成信号级联，延迟ERK激活TGF-β 1有助于减少黑素合成通过MITF下调。(C)2003 Elsevier Ltd.保留所有权利。
Transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in cell proliferation, differentiation, and apoptosis. In this study, we investigated the effects of TGF-beta1 on melanogenesis using a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that TGF-beta1 significantly inhibits melanin synthesis in a concentration-dependent manner and that it reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. We also found that TGF-beta1 reduces microphthalmia-associated transcription factor (MITF) promoter activity and decreased MITF, tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 protein production. In addition, TGF-beta1 was found to induce a delay in the activation of extracellular signal-regulated kinase (ERK) at 6 h, whereas many growth factors activate ERK transiently in minutes. Moreover, the specific ERK pathway inhibitor, PD98059 blocked the hypopigmenting effects induced by TGF-beta1. PD98059 was also found to abrogate the TGF-beta1-mediated down-regulation of MITF, tyrosinase, TRP-1, and TRP-2 production. These results suggest that the ERK pathway may be involved in the melanogenic signaling cascade, and that delayed ERK activation by TGF-beta1 contributes to reduced melanin synthesis via MITF down-regulation. (C) 2003 Elsevier Ltd. All rights reserved.