title: Neurogenic differentiation factor NeuroD confers protection against radiation-induced intestinal injury in mice.
abstract: 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.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Aonan
authors.initials: A
authors.lastname: Du
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Yanchao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Han
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Transfusion Medicine, The General Hospital of the PLA Rocket Force, Beijing 100088, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Chun-Gen
authors.initials: CG
authors.lastname: Xing
authors.affiliation: Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.|Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011832:Radiation Injuries / Q000378:metabolism*; D011839:Radiation, Ionizing; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; C485184:enhanced green fluorescent protein; C093564:Neurogenic differentiation factor 1