Molecular Mechanism of Acute Radiation Enteritis Revealed Using Proteomics and Biological Signaling Network Analysis in Rats
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Background and Aims
Radiation enteritis (RE) has emerged as a significant complication that can progress to severe gastrointestinal disease and the mechanisms underlying its genesis remain poorly understood. The aim of this study was to identify temporal changes in protein expression potentially associated with acute inflammation and to elucidate the mechanism underlying radiation enteritis genesis.
Male Sprague–Dawley rats were irradiated in the abdomen with a single dose of 10 Gy to establish an in vivo model of acute radiation enteritis. Two-dimensional fluorescence difference gel electrophoresis, matrix-assisted laser desorption/ionization time-of-flight spectrometer (MALDI-TOF) tandem mass spectrometry, and peptide mass fingerprinting were used to determine differentially expressed proteins between normal and inflamed intestinal mucosa. Additionally, differentially expressed proteins were evaluated by KO Based Annotation System to find the biological functions associated with acute radiation enteritis.
Intensity changes of 86 spots were detected with statistical significance (ratio ≥ 1.5 or ≤ 1.5, P < 0.05). Sixty one of the 86 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. These radiation-induced proteins with biological functions showed that the FAS pathway and glycolysis signaling pathways were significantly altered using the KOBAS tool.
Our results reveal an underlying mechanism of radiation-induced acute enteritis, which may help clarify the pathogenesis of RE and point to potential targets for therapeutic interventions.
KeywordsRadiation enteritis Proteomics Signaling network Molecular mechanisms
This study was partly supported by the Guangdong Provincial Key Scientific Research Grants (10251008901000008, L Wang), the National Natural Scientific Foundation of China Grants (81072042, L Wang; 81172040, JP Wang), and grants by ”985 project” of Sun Yat-Sen University and Guangdong Translational Medicine Public Platform (4202037) and Sun Yat-Sen Graduate Innovative Personnel Training Funded Projects (Shunxin Song and Jianping Wang). We thank Ms. Biyan Lu, Peihuang Wu, Dr. Kunhua Hu and Chuangyu Wen for their laboratory assistance.
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.