24-Hour Rhythm of Aquaporin-3 Function in the Epidermis Is Regulated by Molecular Clocks
24-Hour Rhythm of Aquaporin-3 Function in the Epidermis Is Regulated by Molecular Clocks
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DOI：
10.1038/jid.2014.13
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发表时间：
2014-06-01
影响因子：
6.5
通讯作者：
Ohdo, Shigehiro
中科院分区：
文献类型：
--
作者：
Matsunaga, Naoya;Itcho, Kazufumi;Ohdo, Shigehiro
水通道蛋白3（AQP 3）位于表皮基底层，调节皮肤的生物学功能，如含水量和经表皮水分流失。最近的一项研究表明，皮肤的生物功能呈现24小时节律，但对这种变化的分子机制仍然知之甚少。在这里，我们表明，在核心时钟组件时钟（Clk/Clk）突变的小鼠显示角质层水合作用降低。对潜在原因的广泛研究使我们将AQP 3确定为控制皮肤生物功能24小时变化的新调节剂。在野生型小鼠表皮中，mAqp 3表现出昼夜节律;然而，这些在Clk/Clk中显著降低。荧光素酶报告基因分析表明，mAqp 3的转录被激活的D-位点结合蛋白，时钟基因。人同源物hAQP 3在与含有50%血清的培养基同步的人角质形成细胞（HaCaT）中也表现出显著的振荡，并且这种节律由内源性CLOCK/BMAL 1异源二聚体调节。这些数据表明，尽管mAqp 3和hAQP 3节律性表达的分子机制不同，但时钟基因参与了时间依赖性皮肤水合作用。我们目前的研究结果提供了小鼠背部皮肤和HaCaT细胞中生物钟和AQP 3功能之间的分子联系。
Aquaporin 3 (AQP3) is located in the basal layer of the epidermis and regulates biological functions of skin such as water content and trans-epidermal water loss. A recent study showed that the biological function of skin exhibits a 24-hour rhythm, but the molecular mechanism of the variation remains poorly understood. Here we show that mice mutated in the core clock component CLOCK (Clk/Clk) show decreased stratum corneum hydration. An extensive search for the underlying cause led us to identify AQP3 as a new regulator to control the 24-hour variation in biological functions of skin. In mouse epidermis of wild-type mice, mAqp3 exhibits circadian rhythms; however, these are significantly decreased in Clk/Clk. Luciferase reporter gene analysis revealed that transcription of mAqp3 is activated by D-site-binding protein, a clock gene. A human homolog, hAQP3, also exhibited significant oscillation in human keratinocyte (HaCaT) cells synchronized with medium containing 50% serum, and this rhythm was regulated by the endogenous CLOCK/BMAL1 heterodimer. These data indicate that although the molecular mechanisms underlying the rhythmic expression of mAqp3 and hAQP3 are different, clock genes are involved in time-dependent skin hydration. Our current findings provide a molecular link between the circadian clock and AQP3 function in mouse dorsal skin and HaCaT cells.