Arsenic-mediated hyperpigmented skin via NF-kappa B/Endothelin1 signaling in an originally developed hairless mouse model.
Arsenic-mediated hyperpigmented skin via NF-kappa B/Endothelin1 signaling in an originally developed hairless mouse model.
复制标题
在最初开发的无毛小鼠模型中，砷通过 NF-kappa B/Endothelin1 信号传导介导皮肤色素沉着过度。
DOI：
10.1007/s00204-017-1975-0
复制
发表时间：
2017
期刊：
影响因子：
6.1
通讯作者：
Kato M.
中科院分区：
文献类型：
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作者：
Yajima I;Kumasaka MY;Iida M;Osino R;Tanihata H;Al Hossain A MM;Ohgami N;Kato M.
长期接触砷与人类的各种疾病有关。皮肤色素沉着是砷中毒患者最敏感的客观症状。然而，关于体内砷介导的皮肤色素沉着的机制的信息非常有限。在这项研究中，毛发杂合子小鼠(HR/HR-小鼠)饮用含3和30微米砷的水两个月后出现皮肤色素沉着，皮肤中砷水平和黑素细胞数量增加。由于人类有可能暴露于井水中3微米的砷，我们的结果表明，Hr/HR-小鼠可能是一种灵敏地反映砷介导的皮肤色素沉着的新模型。然后我们分析了砷引起皮肤色素沉着的机制。Hr/HR-小鼠和人HaCaT皮肤角质形成细胞分别暴露于砷2个月和4个月后，通过核因子-kappaB的激活，其表皮内皮素-1(ET-1)的表达水平增加了5.4-21.5倍。砷和ET-1共同作用于原代正常人上皮黑素细胞，可促进其增殖和黑素合成，并增加MITF-M和ET-1受体的表达。我们的结果表明，皮肤中角质形成细胞和黑素细胞之间通过ET-1及其受体的相互作用有助于砷介导的皮肤色素沉着，这是砷中毒的一个标志。
Chronic exposure to arsenic is associated with various diseases in humans. Skin hyperpigmentation is the most sensitive objective symptom for patients with arsenicosis. However, there is very limited information about the mechanism of arsenic-mediated skin hyperpigmentation in vivo. In this study,hairlesshomozygous mice (Hr/Hr-mice) that drank water containing 3 and 30 µM arsenic for 2 months developed skin hyperpigmentation with increased levels of arsenic and number of melanocytes in the skin. Since it is possible for humans to be exposed to 3 µM of arsenic in well drinking water, our results suggest that theHr/Hr-mice could be a novel model sensitively reflecting arsenic-mediated skin hyperpigmentation. We then analyzed the mechanism of arsenic-mediated skin hyperpigmentation. The epidermis ofHr/Hr-mice and human HaCaT skin keratinocytes exposed to arsenic for 2 and 4 months, respectively, showed 5.4–21.5-fold increased levels of endothelin-1 (ET-1) expression via NF-kappa B activation. Coexposure of primary normal human epithelial melanocytes to arsenic and ET-1 activated their proliferation and melanin synthesis with increased levels of MITF-M and ET-1 receptor expression. Our results suggest that interaction between keratinocytes and melanocytes in the skin through ET-1 and its receptor contributes to arsenic-mediated skin pigmentation, a hallmark of arsenicosis.