Opsin 5 is a key regulator of ultraviolet radiation-induced melanogenesis in human epidermal melanocytes.
Opsin 5 is a key regulator of ultraviolet radiation-induced melanogenesis in human epidermal melanocytes.
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DOI：
10.1111/bjd.19797
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Lan Y;Zeng W;Dong X;Lu H
人类皮肤经常暴露在太阳紫外线辐射 (UVR) 下，具有独特的反应能力，可以在人类表皮黑色素细胞 (HEM) 黑色素生成驱动的保护过程中增加色素沉着。然而，HEM 用于检测和响应 UVR 的分子机制仍不清楚。研究视蛋白 5 (OPN5)（一种对 UVR 波长敏感的光感受器）在 HEM 黑素生成中的功能和潜在机制。使用NaOH法测定HEM中的黑色素含量，并使用l-DOPA法测定酪氨酸酶（TYR）（黑色素合成的关键酶）的活性。通过逆转录定量聚合酶链反应 (RT-qPCR)、蛋白质印迹和免疫荧光检测 UVR 处理与未处理的 HEM 和外植体组织中的 OPN5 表达。使用短干扰 RNA 介导的 OPN5 敲低和慢病毒 OPN5 过表达模型来检查它们各自在 UVR 下对 TYR、酪氨酸酶相关蛋白 1 (TRP1)、TRP2 和小眼相关转录因子 (MITF) 表达的影响。通过RT-qPCR和Western blot检测OPN5表达水平变化引起的TYR、TRP1和TRP2表达变化。此外，还检测了信号通路蛋白的变化。我们发现 OPN5 是 HEM 中负责 UVR 诱导黑素生成的关键传感器。 OPN5 诱导的黑素生成需要 Ca2+ 依赖性 G 蛋白偶联受体和蛋白激酶 C 信号转导，从而有助于 UVR 诱导的 MITF 反应以介导下游细胞效应，并为 OPN5 在哺乳动物光转导中的功能提供证据。值得注意的是，OPN5 激活对于 UVR 诱导的细胞黑色素增加是必要的，并且在黑色素细胞黑色素生成中具有固有的功能。我们的研究结果提供了对黑素细胞中紫外线传感和光转导的分子机制的深入了解，并可能揭示预防色素沉着或色素疾病的分子靶点。 关于这个主题已有哪些已知信息？ 紫外线辐射 (UVR) 会诱导人表皮黑素细胞 (HEM) 对由黑色素合成介导的 DNA 损伤产生保护性反应。酪氨酸酶（TYR）以及酪氨酸酶相关蛋白（TRP1、TRP2）是黑色素合成的关键酶。小眼相关转录因子调节黑素细胞发育和分化的关键基因，并可以通过激活 TYR 和其他色素沉着基因（包括 TRP1）的转录来刺激黑素生成。已知视蛋白 5 (OPN5) 充当对近紫外光谱中的波长做出响应的光感受器。 UVR 通过 OPN5 诱导 HEM 中的黑色素生成。 OPN5 通过钙依赖性 G 蛋白偶联和蛋白激酶 C 信号通路调节 TYR、TRP1 和 TRP2 的表达。 OPN5 在 HEM 中具有介导黑色素生成的固有作用。 这项研究增加了什么？ OPN5 被发现是人类皮肤黑素细胞中 UVR 诱导黑素生成的关键传感器。它可能成为早期治疗色素沉着或色素疾病的目标，以提供更加个性化和经济可行的方法。 翻译信息是什么？ 链接评论：L.V.M.德阿西斯和 A.M.德劳罗·卡斯特鲁奇。 Br J Dermatol 2021； 185：249-250。在线提供简单语言摘要
Human skin, which is constantly exposed to solar ultraviolet radiation (UVR), has a unique ability to respond by increasing its pigmentation in a protective process driven by melanogenesis in human epidermal melanocytes (HEMs). However, the molecular mechanisms used by HEMs to detect and respond to UVR remain unclear. To investigate the function and potential mechanism of opsin 5 (OPN5), a photoreceptor responsive to UVR wavelengths, in melanogenesis in HEMs. Melanin content in HEMs was determined using the NaOH method, and activity of tyrosinase (TYR) (a key enzyme in melanin synthesis) was determined by the l‐DOPA method. OPN5 expression in UVR‐treated vs. untreated HEMs and explant tissues was detected by reverse‐transcription quantitative polymerase chain reaction (RT‐qPCR), Western blotting and immunofluorescence. Short interfering RNA‐mediated OPN5 knockdown and a lentivirus OPN5 overexpression model were used to examine their respective effects on TYR, tyrosinase‐related protein 1 (TRP1), TRP2 and microphthalmia‐associated transcription factor (MITF) expression, under UVR. Changes in expression of TYR, TRP1 and TRP2 caused by changes in OPN5 expression level were detected by RT‐qPCR and Western blot. Furthermore, changes in signalling pathway proteins were assayed. We found that OPN5 is the key sensor in HEMs responsible for UVR‐induced melanogenesis. OPN5‐induced melanogenesis required Ca2+‐dependent G protein‐coupled receptor‐ and protein kinase C signal transduction, thus contributing to the UVR‐induced MITF response to mediate downstream cellular effects, and providing evidence of OPN5 function in mammalian phototransduction. Remarkably, OPN5 activation was necessary for UVR‐induced increase in cellular melanin and has an inherent function in melanocyte melanogenesis. Our results provide insight into the molecular mechanisms of UVR sensing and phototransduction in melanocytes, and may reveal molecular targets for preventing pigmentation or pigment diseases. What is already known about this topic? Ultraviolet radiation (UVR) induces a protective response to DNA damage mediated by melanin synthesis in human epidermal melanocytes (HEMs). Tyrosinase (TYR), with tyrosinase‐related proteins (TRP1, TRP2), are the key enzymes for melanin synthesis. Microphthalmia‐associated transcription factor regulates key genes for melanocyte development and differentiation, and can stimulate melanogenesis by activating transcription of TYR and other pigmentation genes, including TRP1. Opsin 5 (OPN5) is known to function as a photoreceptor responsive to wavelengths in the near UV spectrum. UVR induces melanogenesis in HEMs via OPN5. OPN5 regulates expression of TYR, TRP1 and TRP2 through the calcium‐dependent G protein‐coupled and protein kinase C signalling pathways. OPN5 has an inherent role in HEMs in mediating melanogenesis. What does this study add? OPN5 was discovered as a key sensor for UVR‐induced melanogenesis in human skin melanocytes. It could be a target for early treatment of pigmentation or pigment diseases, to provide a more personalized and economically feasible method. What is the translational message? Linked Comment: L.V.M. de Assis and A.M. de Lauro Castrucci. Br J Dermatol 2021; 185:249–250. Plain language summary available online
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DOI：
10.1073/pnas.1006393107
发表时间：
2010-08-24
影响因子：
11.1
作者：
Nakane, Yusuke;Ikegami, Keisuke;Yoshimura, Takashi
通讯作者：
Yoshimura, Takashi
影响因子：
64.5
作者：
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通讯作者：
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影响因子：
10.3
作者：
Lan, Y.;Wang, Y.;Lu, H.
通讯作者：
Lu, H.
影响因子：
3
作者：
Ahn, Joo Hee;Jin, Sun Hee;Kang, Hee Young
通讯作者：
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影响因子：
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作者：
Hwang, Young Sun;Oh, Sae Woong;Lee, Jongsung
通讯作者：
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