Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts
Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts
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DOI：
10.1007/s11010-008-9736-2
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发表时间：
2008-04
影响因子：
4.3
通讯作者：
Y. Qu;M. Mao;Xihong Li;Yanyou Liu;Jianming Ding;Zhou Jiang;C. Wan;Lin Zhang;Zhengrong Wang
中科院分区：
文献类型：
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作者：
Y. Qu;M. Mao;Xihong Li;Yanyou Liu;Jianming Ding;Zhou Jiang;C. Wan;Lin Zhang;Zhengrong Wang
在外周生物钟中，昼夜节律信号与外界刺激或视交叉上核刺激的同步对于维持人体的正常功能是必不可少的。然而，衰老会破坏外周昼夜节律的同步，从而导致一些与年龄相关的疾病。到目前为止，人们对衰老细胞振荡节律的改变知之甚少。最近的一份报告显示，人血管平滑肌细胞（HSMCs）的细胞衰老通过节律基因表达的失调改变了昼夜节律。此外，这种改变可以通过端粒酶重建来逆转。为了测试端粒酶重建是否可以恢复其他类型衰老细胞中被破坏的昼夜节律，我们使用成纤维细胞作为细胞模型，以深入研究细胞衰老和昼夜节律调节之间的关系。我们发现衰老成纤维细胞对血清刺激的节律性基因表达反应明显减弱，端粒酶重建的成纤维细胞重置了节律性基因表达的昼夜振荡，pERK-CREB和p38-CREB通路的激活可能参与了昼夜节律重置。这些结果表明，端粒酶重建可能是一个很好的方式来重置同步的外周昼夜节律中断衰老组织。
The synchronization of the circadian signals to external or suprachiasmatic nucleus stimulation in the peripheral clocks is essential for maintaining the usual function of human body. However, aging will disrupt the synchronization of peripheral circadian rhythms, thus leading to some age-associated diseases. Up to now, little is known about the modification of the oscillatory rhythms in aged cells. A recent report showed that cell senescence in vascular human smooth muscle cells (HSMCs) altered circadian rhythms by a dysregulation of rhythmic gene expression. Furthermore, this alteration could be reversed by telomerase reconstitution. To test whether telomerase reconstitution can restore disrupted circadian rhythm in other types of senescent cells, we used fibroblasts as cell models to profoundly investigate the relationship between cell senescence and circadian rhythm modulation. We found that the response of rhythmic gene expression to serum stimulation was markedly attenuated in senescent fibroblasts, telomerase-reconstituted fibroblasts reset the circadian oscillation of rhythmic gene expression, and the activation of pERK-CREB and p38-CREB pathways might be involved in the circadian rhythm resetting. These findings suggested that telomerase reconstitution might be a good way to reset synchronization of peripheral circadian rhythms disrupted in senescent tissues.