來自德國柏林查瑞特醫(yī)學(xué)院(Charité-Universitätsmedizin Berlin)的一個研究小組發(fā)現(xiàn)人皮膚有負責(zé)在時間的基礎(chǔ)上操縱它修復(fù)和再生的內(nèi)部時鐘,。2012年7月3日，研究小組把研究成果發(fā)表在PNAS期刊上,。
依據(jù)一天不同的時間,，霜凍、高溫,、太陽光和濕氣對人皮膚產(chǎn)生不同的影響,。如今，研究人員發(fā)現(xiàn)皮膚能夠適應(yīng)這些時間相關(guān)的環(huán)境條件,。研究人員在一天不同的時間從年輕且健康的實驗參與人員皮膚最外層中提取細胞樣品(角質(zhì)形成細胞),。
對角質(zhì)形成細胞的許多種基因進行分析，結(jié)果表明一種生物鐘調(diào)節(jié)用于再生和修復(fù)皮膚細胞的重要性因子,。在這些因子當(dāng)中,，一種被稱作Krüppel樣因子9(Krüppel-like-factor 9, Klf9)的因子延緩角質(zhì)形成細胞發(fā)生細胞分裂。當(dāng)研究人員降低這種因子的活性時,，他們觀察到這種皮膚細胞培養(yǎng)物能夠更加快速地生長,。另一方面，增加Klf9活性與更加緩慢的細胞分裂相關(guān)聯(lián),。與此同時,，這項研究證實應(yīng)激激素皮質(zhì)醇也能夠控制Klf9活性，因而能夠在諸如牛皮癬之類的常見皮膚疾病中發(fā)揮著醫(yī)療效果,。
在皮膚中,，生物鐘的功能就是控制諸如細胞分裂、細胞分化和DNA修復(fù)之類的多種過程的精準(zhǔn)定時,。Kramer 教授認為,，只要他們能夠更好地理解這些過程，那么他們就能夠在一天當(dāng)中某個時間使用藥物,，這樣藥物就發(fā)揮出最好的療效,，同時使得它的副作用最小化。(生物谷：Bioon.com)
本文編譯自Skin has an internal clock: study
doi: 10.1073/pnas.1118641109
PMC:
PMID:
Krüppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes
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.
