2. Academic Validation
  3. 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

  • Free Radic Biol Med. 2018 Dec;129:446-453. doi: 10.1016/j.freeradbiomed.2018.10.423.
Chao Bian 1,  Wen-Jun Qin 2,  Cui-Ying Zhang 3,  Guan-Lian Zou 2,  Yong-Zhao Zhu 4,  Juan Chen 5,  Ren Zhao 3,  Yan-Yang Wang 6,  Hong Zhe 7
Affiliations

Affiliations

  • 1 Graduate School, Ningxia Medical University, Yinchuan 750004, Ningxia, China; Dept. of Radiation Oncology, Inner Mongolia People's Hospital, Hohhot 010017, Inner Mongolia, China.
  • 2 Graduate School, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
  • 3 Dept. of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China; Cancer Institute, Ningxia Medical University, Yinchuan 750004, Ningxia, China.
  • 4 Surgical Laboratory, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China.
  • 5 Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China.
  • 6 Dept. of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China; Cancer Institute, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: wangyy@nxmu.edu.cn.
  • 7 Dept. of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China; Cancer Institute, Ningxia Medical University, Yinchuan 750004, Ningxia, China. Electronic address: zheh@nxmu.edu.cn.
PMID: 30339882 DOI: 10.1016/j.freeradbiomed.2018.10.423
Abstract

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‑β (TGF‑β)/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-β/SMAD3 pathway, suggesting THD as a potential novel agent for RILF prevention.

Keywords

Mice; Nrf2; Radiation-induced lung fibrosis; TGF‑β/Smad3 signaling pathway; Thalidomide.

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