Zhang Yuehua,Liu Hangfeng,Zhang Shuyu,et al.Proteomic analysis of radiation-induced esophagitis in rats[J].Chinese Journal of Radiological Medicine and Protection,2024,44(9):725-733
Proteomic analysis of radiation-induced esophagitis in rats
Received:January 03, 2024  
DOI:10.3760/cma.j.cn112271-20240103-00003
KeyWords:Radiation-induced esophagitis  Tandem mass tag  Labeled quantitative proteomics  Functional enrichment analysis  Differentially expressed protein
FundProject:国家自然科学基金(82304078,82003390);四川省自然科学基金面上项目(2024NSFSC0764);中央引导地方科技发展资金自由探索基础研究(2023ZYD0084);四川大学辐射物理及技术教育部重点实验室开放课题(2023SCURPTO3,2023SCURPT07);成都医学院-成都医学院第二附属医院联合基金(2022LHFSZYB-01);中核集团青年英才项目(CNNC202379)
Author NameAffiliationE-mail
Zhang Yuehua The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu 610051, China
Laboratory of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China 
 
Liu Hangfeng The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu 610051, China
Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China 
 
Zhang Shuyu The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu 610051, China
Laboratory of Radiation Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China
Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China 
 
Du Mengjie Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Meng Xiaochen Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Tu Wenling The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu 610051, China tu.wenling@foxmail.com 
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Abstract::
      Objective To investigate the impacts of ionizing radiation on protein expression profiles in esophageal tissues of rats using quantitative proteomics, in order to reveal the molecular mechanisms underlying the onset and development of radiation-induced esophagitis (RIE). Methods A total of twenty-four male SD rats were divided by simple randomization into three groups: the control, 25 Gy irradiation, and 35 Gy irradiation groups, and their esophageal tissues were collected at 7 d post-irradiation to extract total protein. Then, changes in the protein expression profiles of the esophageal tissues in irradiated rats were investigated using tandem mass tag (TMT)-labeled quantitative proteomics and bioinformatics analysis. Additionally, the expressions of two key proteins, Hp and Ndufs4, were validated using immunohistochemistry and Western blot. Results A comparison with the control group revealed a total of 847 differentially expressed proteins (DEPs; 483 up-regulated and 364 down-regulated) following 25 Gy irradiation and 699 DEPs (443 up-regulated and 256 down-regulated) following 35 Gy irradiation. Different radiation doses led to common 326 up-regulated proteins, which were mainly involved in biological processes and signaling pathways related to immune and inflammatory responses, and 210 down-regulated proteins, which were primarily involved in biological processes and signaling pathways related to energy production and metabolism. Furthermore, a total of 155 proteins were screened using a constructed protein protein interaction(PPI) network. Of these proteins, the up-regulated ones were most associated with three functional pathways, namely innate immune responses, complement and coagulation cascades, and innate immune system, while the down-regulated ones were most associated with energy acquisition via oxidizing organic compounds, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle and respiratory electron transfer. These functions were enriched with nine complement-related up-regulated and five mitochondria-related down-regulated proteins, respectively. Ionizing radiation significantly up-regulated Hp (t= 27.94, 10.96, P<0.001) and down-regulated Ndufs4 (t= 59.27, 54.07, P<0.001), consistent with the protein sequencing result. Conclusions Ionizing radiation can change the protein expression profiles in the esophageal tissues of rats, and these DEPs are involved in multiple radiobiology-related functional pathways such as immune processes, inflammatory responses, and abnormal energy metabolism. Screening and validation of key proteins are helpful for identifying potential biomarkers of radiation-induced esophagitis.
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