Protein and miRNA profiling of radiation-induced skin injury in rats: the protective role of peroxiredoxin-6 against ionizing radiation
Protein and miRNA profiling of radiation-induced skin injury in rats: the protective role of peroxiredoxin-6 against ionizing radiation
复制标题
大鼠辐射引起的皮肤损伤的蛋白质和 miRNA 分析：peroxiredoxin-6 对电离辐射的保护作用。
DOI：
10.1016/j.freeradbiomed.2014.01.019
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发表时间：
2014-04-01
影响因子：
7.4
通讯作者：
Ding, Wei-Qun
中科院分区：
文献类型：
--
作者：
Zhang, Shuyu;Wang, Wenjie;Ding, Wei-Qun
放射引起的皮肤损伤是放射治疗期间的一个严重问题。然而，辐射引起的皮肤损伤发病机制的分子机制尚未得到广泛报道。大多数生物功能是由蛋白质和非编码 RNA（包括 microRNA (miRNA)）执行和调节的。 mRNA 和 miRNA 之间的相互作用与疾病的发生和进展有关。基因组学和蛋白质组学的技术进步使得我们能够探索疾病的病因，并有可能扩大我们对辐射引起的皮肤损伤的分子发病机制的理解。在本研究中，我们将 45 Gy 电子束照射的大鼠皮肤中蛋白质和 miRNA 的表达与邻近正常组织的表达进行了比较。我们在受辐射的皮肤中发现了 24 种优先表达的蛋白质和 12 种失调的 miRNA。通过使用生物信息学工具分析蛋白质和 miRNA 谱，我们确定了 miR-214 和 peroxiredoxin-6 (PRDX-6) 之间可能存在的相互作用。接下来，我们研究了 PRDX-6 的表达及其失调的后果。 PRDX-6 被辐射诱导的 miR-214 抑制，并参与辐射引起的皮肤损伤的发病机制。 PRDX-6 的过度表达赋予细胞放射抗性，减少细胞凋亡，并在辐射暴露后保持线粒体完整性。此外，PRDX-6 体内转染可降低辐射诱导的活性氧和丙二醛浓度，并改善辐射诱导的大鼠皮肤损伤。我们目前的研究结果说明了辐射引起的皮肤损伤期间的分子变化以及 PRDX-6 在改善大鼠这种损伤中的重要作用。 (c) 2014 Elsevier Inc. 保留所有权利。
Radiation-induced skin injury is a serious concern during radiotherapy. However, the molecular mechanism underlying the pathogenesis of radiation-induced skin injury has not been extensively reported. Most biological functions are performed and regulated by proteins and noncoding RNAs, including microRNAs (miRNAs). The interplay between mRNA and miRNA has been implicated in disease initiation and progression. Technical advances in genomics and proteomics have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathogenesis of radiation-induced skin injury. In this study, we compared the protein and miRNA expression in rat skin irradiated with a 45-Gy electron beam with expression from adjacent normal tissues. We found 24 preferentially expressed proteins and 12 dysregulated miRNAs in irradiated skin. By analyzing the protein and miRNA profiles using bioinformatics tools, we identified a possible interaction between miR-214 and peroxiredoxin-6 (PRDX-6). Next, we investigated the expression of PRDX-6 and the consequences of its dysregulation. PRDX-6 is suppressed by radiation-inducible miR-214 and is involved in the pathogenesis of radiation-induced skin injury. Overexpression of PRDX-6 conferred radioresistance on cells, decreased cell apoptosis, and preserved mitochondrial integrity after radiation exposure. In addition, in vivo transfection with PRDX-6 reduced radiation-induced reactive oxygen species and the malondialdehyde concentration and ameliorated radiation-induced skin damage in rats. Our present findings illustrate the molecular changes during radiation-induced skin injury and the important role of PRDX-6 in ameliorating this damage in rats. (c) 2014 Elsevier Inc. All rights reserved.