Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice.
Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice.
复制标题
神经源性分化因子 NeuroD 可以保护小鼠免受辐射引起的肠道损伤
DOI：
10.1038/srep30180
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发表时间：
2016-07-20
影响因子：
4.6
通讯作者：
Cao J
中科院分区：
文献类型：
--
作者：
Li M;Du A;Xu J;Ma Y;Cao H;Yang C;Yang XD;Xing CG;Chen M;Zhu W;Zhang S;Cao J
The gastrointestinal tract, especially the small intestine, is particularly sensitive to radiation and is prone to radiation-induced injury as a result. Neurogenic differentiation factor (NeuroD) is an evolutionarily-conserved basic helix-loop-helix (bHLH) transcription factor. NeuroD contains a protein transduction domain (PTD), which allows it to be exogenously delivered across the membrane of mammalian cells, whereupon its transcription activity can be unleashed. Whether NeuroD has therapeutic effects for radiation-induced injury remains unclear. In the present study, we prepared a NeuroD-EGFP recombinant protein and explored its protective effects on the survival and intestinal damage induced by ionizing radiation. Our results showed that NeuroD-EGFP could be transduced into small intestine epithelial cells and tissues. NeuroD-EGFP administration significantly increased overall survival of mice exposed to lethal total body irradiation (TBI). This recombinant NeuroD also reduced radiation-induced intestinal mucosal injury and apoptosis and improved crypt survival. Expression profiling of NeuroD-EGFP-treated mice revealed upregulation of tissue inhibitor of metalloproteinase 1 (TIMP-1), a known inhibitor of apoptosis in mammalian cells. In conclusion, NeuroD confers protection against radiation-induced intestinal injury and provides a novel therapeutic clinical option for the prevention of intestinal side effects of radiotherapy and the treatment of victims of incidental exposure.
