Exposure to ionizing radiation results in injuries of the hematopoietic, gastrointestinal, and respiratory systems, which are the leading causes responsible for morbidity and mortality. Gastrointestinal injury occurs as an acute radiation syndrome. To help inform on the natural history of the radiation-induced injury of the partial body irradiation model, we quantitatively profiled the proteome of jejunum from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Jejunum was analyzed by liquid chromatography-tandem mass spectrometry, and pathway and gene ontology analysis were performed. A total of 3,245 unique proteins were quantified out of more than 3,700 proteins identified in this study. Also a total of 289 proteins of the quantified proteins showed significant and consistent responses across at least three time points post-irradiation, of which 263 proteins showed strong upregulations while 26 proteins showed downregulations. Bioinformatic analysis suggests significant pathway and upstream regulator perturbations post-high dose irradiation and shed light on underlying mechanisms of radiation damage. Canonical pathways altered by radiation included GP6 signaling pathway, acute phase response signaling, LXR/RXR activation, and intrinsic prothrombin activation pathway. Additionally, we observed dysregulation of proteins of the retinoid pathway and retinoic acid, an active metabolite of vitamin A, as quantified by liquid chromatography-tandem mass spectrometry. Correlation of changes in protein abundance with a well-characterized histological endpoint, corrected crypt number, was used to evaluate biomarker potential. These data further define the natural history of the gastrointestinal acute radiation syndrome in a non-human primate model of partial body irradiation with minimal bone marrow sparing.

中文翻译：

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对非人类灵长类动物局部照射模型中胃肠道急性放射综合征自然史的蛋白质组学评估，包括对维甲酸通路的失调。

暴露于电离辐射会导致造血系统、胃肠道和呼吸系统受损，而这些系统是导致发病率和死亡率的主要原因。胃肠道损伤以急性放射综合征的形式发生。为了帮助了解部分身体照射模型的辐射损伤的自然史，我们在 12 Gy 部分身体照射和 2.5% 的骨髓在 3周。通过液相色谱-串联质谱分析空肠，并进行通路和基因本体分析。在本研究中鉴定的 3,700 多种蛋白质中，共有 3,245 种独特蛋白质被量化。此外，在辐照后至少三个时间点，共有 289 种蛋白质显示出显着且一致的反应，其中 263 种蛋白质表现出强烈的上调，而 26 种蛋白质表现出下调。生物信息学分析表明，高剂量辐照后存在显着的通路和上游调节剂扰动，并揭示了辐射损伤的潜在机制。辐射改变的典型通路包括 GP6 信号通路、急性期反应信号通路、LXR/RXR 激活和内在凝血酶原激活通路。此外，我们观察到通过液相色谱-串联质谱法量化的类视黄醇途径蛋白质和维甲酸（维生素 A 的活性代谢物）的失调。蛋白质丰度变化与特征明确的组织学终点、校正的隐窝数的相关性用于评估生物标志物的潜力。这些数据进一步定义了非人类灵长类动物局部照射模型中胃肠道急性放射综合征的自然史，骨髓保留最少。