Control of senescence by CXCR2 and its ligands
Control of senescence by CXCR2 and its ligands
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DOI：
10.4161/cc.7.19.6780
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发表时间：
2008-10-01
期刊：
影响因子：
4.3
通讯作者：
Gil, Jesus
中科院分区：
文献类型：
--
作者：
Acosta, Juan C.;O'Loghlen, Ana;Gil, Jesus
衰老是一种不可逆的生长停滞，具有重要的生理意义，因为它有助于抑制肿瘤，并可能在衰老中发挥作用。在衰老过程中，细胞会发生深刻的表型变化，影响细胞形态和染色质结构等。衰老细胞也会经历显着的转录变化，例如大量不同分泌因子的产生增加，这是所谓的衰老相关分泌表型的基础。虽然其中一些因子先前已被证明具有不同的促肿瘤活性，但我们最近证明衰老细胞分泌的 CXCR2 结合趋化因子（例如 IL-8 或 GRO α）有助于通过激活 p53 途径来增强衰老。重要的是，我们的数据补充了几个小组提出的数据，表明衰老过程中分泌的其他因素（如 PAI-1、IGFBP-7 或 IL-6）也有助于衰老反应。在这里，我们在分泌因子通过旁分泌和/或自分泌机制调节衰老的新作用的背景下讨论我们的发现。
Senescence is an irreversible growth arrest with important physiological implications as it contributes to tumour suppression and may have a role in aging. During senescence, cells suffer profound phenotypic changes affecting amongst others cell morphology and chromatin structure. Senescent cells also undergo significant transcriptional changes, such as the increased production of a plethora of different secreted factors, which are the basis of the so-called senescence-associated secretory phenotype. While some of these factors have been previously shown to possess different pro-tumorigenic activities, we recently demonstrated that the secretion of CXCR2-binding chemokines (such as IL-8 or GRO alpha) by senescent cells contribute to reinforce senescence via activation of the p53 pathway. Importantly, our data adds to that presented by several groups suggesting that also other factors secreted during senescence (such as PAI-1, IGFBP-7 or IL-6) contribute to the senescent response. Here, we discuss our findings in the context of the emerging role for secreted factors in regulating senescence through paracrine and/or autocrine mechanisms.