PNAS：人类皮肤也有内部时钟

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来自德国柏林查瑞特医学院(Charité-Universitätsmedizin Berlin)的一个研究小组发现人皮肤有负责在时间的基础上操纵它修复和再生的内部时钟。2012年7月3日，研究小组把研究成果发表在<em>PNAS</em>期刊上。

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依据一天不同的时间，霜冻、高温、太阳光和湿气对人皮肤产生不同的影响。如今，研究人员发现皮肤能够适应这些时间相关的环境条件。研究人员在一天不同的时间从年轻且健康的实验参与人员皮肤最外层中提取细胞样品(角质形成细胞)。

对角质形成细胞的许多种基因进行分析，结果表明一种生物钟调节用于再生和修复皮肤细胞的重要性因子。在这些因子当中，一种被称作Krüppel样因子9(Krüppel-like-factor 9, Klf9)的因子延缓角质形成细胞发生细胞分裂。当研究人员降低这种因子的活性时，他们观察到这种皮肤细胞培养物能够更加快速地生长。另一方面，增加Klf9活性与更加缓慢的细胞分裂相关联。与此同时，这项研究证实应激激素皮质醇也能够控制Klf9活性，因而能够在诸如牛皮癣之类的常见皮肤疾病中发挥着医疗效果。

在皮肤中，生物钟的功能就是控制诸如细胞分裂、细胞分化和DNA修复之类的多种过程的精准定时。Kramer 教授认为，只要他们能够更好地理解这些过程，那么他们就能够在一天当中某个时间使用药物，这样药物就发挥出最好的疗效，同时使得它的副作用最小化。

本文编译自<a href="http://medicalxpress.com/news/2012-07-skin-internal-clock.html" target="_blank">Skin has an internal clock: study</a>
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<a title="" href="http://dx.doi.org/10.1073/pnas.1118641109" target="_blank">doi: 10.1073/pnas.1118641109</a>
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<br/><strong>Krüppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes</strong><br/>


Florian Spörla,b, Sandra Korgea, Karsten Jürchottb, Minetta Wunderskirchnera, Katja Schellenbergb, Sven Heinsa, Aljona Spechta, Claudia Stollc, Roman Klemzb, Bert Maierb, Horst Wencka, Annika Schradera, Dieter Kunzc,d, Thomas Blatta,1, and Achim Kramer

Circadian clocks govern a wide range of cellular and physiological functions in various organisms. Recent evidence suggests distinct functions of local clocks in peripheral mammalian tissues such as immune responses and cell cycle control. However, studying circadian action in peripheral tissues has been limited so far to mouse models, leaving the implication for human systems widely elusive. In particular, circadian rhythms in human skin, which is naturally exposed to strong daytime-dependent changes in the environment, have not been investigated to date on a molecular level. Here, we present a comprehensive analysis of circadian gene expression in human epidermis. Whole-genome microarray analysis of suction-blister epidermis obtained throughout the day revealed a functional circadian clock in epidermal keratinocytes with hundreds of transcripts regulated in a daytime-dependent manner. Among those, we identified a circadian transcription factor, Krüppel-like factor 9 (Klf9), that is substantially up-regulated in a cortisol and differentiation-state-dependent manner. Gain- and loss-of-function experiments showed strong antiproliferative effects of Klf9. Putative Klf9 target genes include proliferation/differentiation markers that also show circadian expression in vivo, suggesting that Klf9 affects keratinocyte proliferation/differentiation by controlling the expression of target genes in a daytime-dependent manner.

<br/>来源：生物谷

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