Telomere length regulates ISG15 expression in human cells
Telomere length regulates ISG15 expression in human cells
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DOI：
10.18632/aging.100066
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发表时间：
2009-07-01
期刊：
影响因子：
5.2
通讯作者：
Wright, Woodring E.
中科院分区：
文献类型：
--
作者：
Lou, Zhenjun;Wei, Jun;Wright, Woodring E.
由端粒长度调控的内源性基因在人类细胞中尚未被发现。本研究表明，端粒长度调节干扰素刺激基因15 （ISG15, 1p36.33）的表达。ISG15的表达（RNA和蛋白）在端粒短的人细胞中升高，在端粒被人端粒酶逆转录酶（hTERT）延长后降低。ISG15的短端粒依赖性上调不是由复制性衰老/DNA损伤信号或I型干扰素介导的。在从不同老年人获得的人体皮肤标本中，ISG15在老年人的一个细胞亚群中上调。我们的研究结果表明，在DNA损伤信号开始之前，内源性人类基因可以通过端粒的长度进行调节，并提示细胞更新/端粒缩短可能提供一种调节细胞生理的机制。ISG15的上调与端粒缩短可能有助于与人类衰老相关的慢性炎症状态。
Endogenous genes regulated by telomere length have not previously been identified in human cells. Here we show that telomere length regulates the expression of interferon stimulated gene 15 (ISG15, 1p36.33). ISG15 expression (RNA and protein) increases in human cells with short telomeres, and decreases following the elongation of telomeres by human telomerase reverse transcriptase (hTERT). The short-telomere-dependent up-regulation of ISG15 is not mediated by replicative senescence/DNA damage signaling or type I interferons. In human skin specimens obtained from various aged individuals, ISG15 is up-regulated in a subset of cells in older individuals. Our results demonstrate that endogenous human genes can be regulated by the length of telomeres prior to the onset of DNA damage signals, and suggest the possibility that cell turnover/telomere shortening may provide a mechanism for adjusting cellular physiology. The upregulation of ISG15 with telomere shortening may contribute to chronic inflammatory states associated with human aging.