Thalidomide (THD) alleviates radiation induced lung fibrosis (RILF) via down-regulation of TGF-β/Smad3 signaling pathway in an Nrf2-dependent manner
Thalidomide (THD) alleviates radiation induced lung fibrosis (RILF) via down-regulation of TGF-β/Smad3 signaling pathway in an Nrf2-dependent manner
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DOI：
10.1016/j.freeradbiomed.2018.10.423
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发表时间：
2018-12-01
影响因子：
7.4
通讯作者：
Zhe, Hong
中科院分区：
文献类型：
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作者：
Bian, Chao;Qin, Wen-Jun;Zhe, Hong
放射性肺纤维化（RILF）是胸部肿瘤患者放射治疗的并发症。沙利度胺（THD）对纤维化和炎症性疾病具有治疗作用。本研究的目的是研究THD对小鼠RILF的治疗效果，并更好地了解治疗效果的潜在调节机制。我们发现THD减轻了小鼠辐射引起的纤维化。THD对RILF的作用与升高低水平的活性氧（ROS）有关，活性氧通过激活核因子（红细胞衍生2）样2（Nrf 2）抑制转化生长因子-β（TGF-β）/Smad 3信号通路。使用Nrf 2-/-小鼠模型分析THD的治疗效果证实了Nrf 2在体内的作用。此外，没有观察到THD对胸癌细胞系的辐射保护作用。总之，这些数据表明，THD减弱小鼠RILF，这是由Nrf 2依赖性下调TGF-β/Smad 3途径介导的，表明THD作为一种潜在的新的RILF预防剂。
Radiation-induced lung fibrosis (RILF) is a complication of radiotherapy in thoracic cancer patients. Thalidomide (THD) has a therapeutic effect on fibrotic and inflammatory disorders. The purpose of the current study was to investigate the therapeutic effect of THD on RILF in mice and better understand the underlying regulatory mechanisms of the therapeutic effect. We found that THD mitigated the fibrosis caused by irradiation in mice. The action of THD on RILF was related to the elevation of low levels reactive oxygen species (ROS), which inhibited the transforming growth factor-beta (TGF-beta)/Smad3 signaling pathway through activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Analysis of the therapeutic effect of THD using Nrf2-/- mouse model confirmed the role of Nrf2 in vivo. In addition, no radioprotective effect of THD on thoracic cancer cell lines was observed. In conclusion, these data showed that THD attenuated RILF in mice, which was mediated by Nrf2-dependent down-regulation of the TGF-beta/Smad3 pathway, suggesting THD as a potential novel agent for RILF prevention.