Jackson Isabel L, Zhang Yuji, Bentzen Søren M, Hu Jingping, Zhang Angel, Vujaskovic Zeljko
Division of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Division of Biostatistics and Bioinformatics, Department of Epidemiology &Public Health, and the Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Sci Rep. 2016 Nov 15;6:36579. doi: 10.1038/srep36579.
Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury.
小鼠品系间辐射诱导的肺损伤发病机制的差异为阐明驱动组织反应从修复和恢复到器官衰竭的分子机制提供了独特的机会。在此，我们利用两种特征明确的放射性肺炎/肺纤维化小鼠模型，比较和对比单次全胸肺照射足以导致轻度至重度发病/死亡后24小时肺组织中的差异基因表达。805个基因的表达作为对辐射的一般反应发生了改变；鉴定出42个基因，其表达与致死阈值相对应。发现三个基因，其表达在致死剂量范围内而非亚致死剂量范围内发生改变。对最有前景的基因抵抗素样分子α的蛋白质产物进行的时间进程分析表明，放射敏感与放射耐受品系之间的表达存在显著差异，表明该蛋白质在急性肺损伤中具有独特作用。
