Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
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DOI：
10.7554/elife.54523
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发表时间：
2020-03-30
期刊：
影响因子：
7.7
通讯作者：
Galderis, Umberto
中科院分区：
文献类型：
--
作者：
Alessio, Nicola;Squillaro, Tiziana;Galderis, Umberto
衰老细胞分泌几种分子，统称为衰老相关分泌表型（senescence associated secretory phenotype， SASP）。在体外化学和物理应激后衰老细胞的SASP中，我们发现IGFBP-4蛋白可以被认为是一种一般的应激介质。这个因子似乎在衰老-旁分泌信号传导中起关键作用。我们提供的证据表明，基因毒性损伤，如低剂量照射，可能促进IGFBP-4在接受100 mGy x射线照射的小鼠和接受计算机断层扫描的人类受试者血液中的释放。循环IGFBP-4水平升高可能与促衰老作用有关。我们发现每周两次腹腔注射IGFBP-4的小鼠肺、心脏和肾脏中的衰老细胞显著增加，持续两个月。然后，我们分析了基因毒性应激源如何促进IGFBP-4的释放，以及与该蛋白诱导衰老相关的分子途径。
Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.