Proteomic analysis of radiation-induced esophagitis in rats
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.
Radiation-induced esophagitisTandem mass tagLabeled quantitative proteomicsFunctional enrichment analysisDifferentially expressed protein
万方数据
维普
