Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity.
Gene Expression Profiles from Heart, Lung and Liver Samples of Total-Body-Irradiated Minipigs: Implications for Predicting Radiation-Induced Tissue Toxicity.
复制标题
DOI：
10.1667/rade-20-00123.1
复制
发表时间：
2020-10-02
影响因子：
3.4
通讯作者：
Aryankalayil MJ
中科院分区：
文献类型：
--
作者：
Chopra S;Moroni M;Martello S;Bylicky M;May J;Hritzo B;MacMillan L;Coleman CN;Aryankalayil MJ
在发生重大意外或故意的辐射照射事件时，受影响的人口可能遭受全身或局部电离辐射照射，急性暴露于器官，可能造成危及生命的伤害。因此，有必要确定能够预测器官特异性损伤的标志物，以便应用适当的定向或包涵治疗。在本工作中，我们在Göttingen迷你猪的心脏、肺和肝脏组织中发现了响应全身照射（TBI）的基因表达变化。各组分别接受1.7、1.9、2.1或2.3 Gy TBI，随访45 d。器官样本在第45天结束时收集，如果动物显示出需要安乐死的疾病，则更早收集。我们的研究结果表明，不同的器官对创伤性脑损伤的反应是非常具体和独特的。我们还发现，就基因表达变化而言，肝脏是受影响最严重的器官，而在非幸存者（存活时间为45天）的肝脏样本中，脂质代谢途径最不受控制。我们确定了器官特异性基因表达特征，可以准确区分非幸存者、幸存者和对照动物，而不考虑辐射后的剂量和时间。这些辐射引起的损伤标记在什么时候显现，以及如何将这些信息用于干预治疗，目前正在研究中。
In the event of a major accidental or intentional radiation exposure incident, the affected population could suffer from total- or partial-body exposures to ionizing radiation with acute exposure to organs that would produce life-threatening injury. Therefore, it is necessary to identify markers capable of predicting organ-specific damage so that appropriate directed or encompassing therapies can be applied. In the current work, gene expression changes in response to total-body irradiation (TBI) were identified in heart, lungs and liver tissue of Göttingen minipigs. Animals received 1.7, 1.9, 2.1 or 2.3 Gy TBI and were followed for 45 days. Organ samples were collected at the end of day 45 or sooner if the animal displayed morbidity necessitating euthanasia. Our findings indicate that different organs respond to TBI in a very specific and distinct manner. We also found that the liver was the most affected organ in terms of gene expression changes, and that lipid metabolic pathways were the most deregulated in the liver samples of non-survivors (survival time,45 days). We identified organ-specific gene expression signatures that accurately differentiated non-survivors from survivors and control animals, irrespective of dose and time postirradiation. At what point did these radiation-induced injury markers manifest and how this information could be used for applying intervention therapies are under investigation.