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The mechanism of radiation-induced senescence and the effect for angiogenesis in endothelial cells

辐射诱导衰老的机制及对内皮细胞血管生成的影响

基本信息

批准号：
18510042
负责人：
MIURA Masahiko
金额：
$ 2.59万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18510042/
关键词：
Endothelial cells Ionizng radiation Senescence-like phenotype Angiogenesis DNA repair

项目摘要

The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. Expression of genes associated with cell cycle progression and DNA replication was remarkably decreased and in vitro invasion and migration activities through Matrigel of these IRSL ECs were significantly suppressed. We also found that confluent ECs exhibited a high frequency IRSL phenotype when replated immediately after irradiation, but incubation in plateau-phase conditions reduced induction of the phenotype and enhanced cell survival as determined by colony formation. DNA double strand breaks (DSB) repair kinetics showed a faster time course in confluent Ecs than in growing Ecs, which may contribute to the protective mechanism of the IRSL phenotype in the former. These results imply that the IRSL phenotype could be an important factor for determining the angiogenic activity of Ecs following irradiation. The present study should shed additional light on understanding the effect of IR on tumor angiogenesis.

电离辐射（IR）对肿瘤血管生成的影响仍然是未知的。在这项研究中，我们发现，IR（8戈伊）诱导的血管内皮细胞（EC）进行指数生长的高频率（80-90%）的衰老样表型。这一发现使我们能够通过检查这些EC的基因表达谱和体外血管生成活性来表征IR诱导的衰老样（IRSL）表型。与细胞周期进程和DNA复制相关的基因的表达显着降低，并在体外侵袭和迁移活动，这些IRSL EC通过基质胶显着抑制。我们还发现，汇合的EC表现出高频率IRSL表型时，照射后立即重新铺板，但在平台期条件下孵育减少诱导的表型和增强细胞存活的集落形成确定。DNA双链断裂（DSB）修复动力学在融合的Ecs中比在生长的Ecs中显示更快的时间过程，这可能有助于前者的IRSL表型的保护机制。这些结果表明，IRSL表型可能是一个重要的因素，为确定血管生成活性的内皮细胞照射后。本研究将进一步阐明IR对肿瘤血管生成的影响。