Tanioka Miki, Yamada Hiroyuki, Doi Masao, Bando Hideki, Yamaguchi Yoshiaki, Nishigori Chikako, Okamura Hitoshi
Division of Dermatology, Kobe University Graduate School of Medicine, Kobe, Japan.
J Invest Dermatol. 2009 May;129(5):1225-31. doi: 10.1038/jid.2008.345. Epub 2008 Nov 27.
Clock genes in the skin exhibit day-night changes in expression; however, whether these changes are brought by external light or intrinsic mechanisms is unclear. In this study, we demonstrated that expression of the clock and clock-controlled genes showed robust rhythms in mouse skin under constant dark conditions, whereas these rhythms were completely lost in Cry1/Cry2 knockout mice lacking a molecular clock. At the cellular level, the main oscillatory protein in the mammalian molecular clock, PER2, was expressed in the nuclei of keratinocytes in the epidermis and hair follicles, with expression peaking at CT16 (subjective dusk), 4-8 hours after expression of its mRNA. These expression patterns in the skin stopped after the ablation of the central clock in the suprachiasmatic nucleus (SCN), which was not recovered even in animals housed in 12 hour-light/12 hour-dark conditions. These findings demonstrate that the intrinsic oscillating molecular clock exists in the epidermis, and that signaling from the SCN is essential for the maintenance of the epidermal clock, and cannot be compensated by external light.
皮肤中的生物钟基因在表达上呈现昼夜变化；然而，这些变化是由外部光线还是内在机制引起的尚不清楚。在本研究中，我们证明在持续黑暗条件下，生物钟基因和生物钟调控基因在小鼠皮肤中表现出强烈的节律性，而在缺乏分子钟的Cry1/Cry2基因敲除小鼠中这些节律完全消失。在细胞水平上，哺乳动物分子钟的主要振荡蛋白PER2在表皮和毛囊的角质形成细胞核中表达，其表达在mRNA表达后4-8小时于CT16（主观黄昏）达到峰值。视交叉上核（SCN）中的中央生物钟被切除后，皮肤中的这些表达模式停止，即使在12小时光照/12小时黑暗条件下饲养的动物中也无法恢复。这些发现表明表皮中存在内在振荡分子钟，并且来自SCN的信号对于维持表皮生物钟至关重要，且不能由外部光线补偿。
