Establishment of a radiation-induced vocal fold fibrosis mouse model
Establishment of a radiation-induced vocal fold fibrosis mouse model
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DOI：
10.1016/j.bbrc.2022.02.065
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发表时间：
2022-02-25
影响因子：
3.1
通讯作者：
Kishimoto, Yo
中科院分区：
文献类型：
--
作者：
Tanigami, Yuki;Kawai, Yoshitaka;Kishimoto, Yo
声带放射后纤维化被认为会导致声音障碍。然而，这种现象发生的机制却鲜有记录，可能是因为缺乏合适的实验动物模型。本研究的目的是建立一个简单且可重复的喉辐射小鼠模型，以研究声带纤维化随时间的发展情况。将 C57BL/6 小鼠单独放置在铅屏蔽中，接受单剂量 20 Gy 的照射。照射后1、2和6个月，采集喉并进行组织学检查和基因表达分析。受照射的声带表现出时间依赖性组织收缩和胶原沉积增加，而透明质酸水平的变化没有显着差异。转录分析显示 6 个月时 TGF-β1 和 iNOS 的表达上调，但 Acta2、Col1a1、Col3a1 和 MMP8 的表达下调。此外，TGF-β1 升高和下游基因表达水平降低表明 TGF-β/Smad 通路中存在抑制因子。胶原蛋白的组织学和转录研究的差异可能表明，辐射引起的声带纤维化可能是由胶原蛋白周转时间延长引起的。总体而言，我们使用简单的方案建立了辐射引起的声带纤维化的小鼠模型。需要进一步的研究来阐明辐射引起的声带纤维化的发病机制。 (c) 2022 Elsevier Inc. 保留所有权利。
Post-radiation fibrosis of the vocal folds is thought to cause vocal impairment. However, the mechanism by which this occurs has been poorly documented, probably because of the lack of an appropriate experimental animal model. The purpose of this study was to establish a simple and reproducible mouse model of laryngeal radiation to investigate the development of vocal fold fibrosis over time. C57BL/6 mice individually placed in a lead shield were irradiated with a single dose of 20 Gy. At 1, 2, and 6 months after irradiation, larynges were harvested and subjected to histological examination and gene expression analysis. Irradiated vocal folds showed time-dependent tissue contraction and increased collagen deposition, with no significant difference in the changes in hyaluronic acid levels. Transcriptional analysis revealed upregulated expressions of TGF-beta 1 and iNOS at 6 months, but downregulated expressions of Acta2, Col1a1, Col3a1, and MMP8. Moreover, elevated TGF-beta 1 and reduced downstream gene expression levels indicated the existence of an inhibitory factor over the TGF-beta/Smad pathway. Discrepancies in histological and transcriptional studies of collagen might suggest that radiation-induced vocal fold fibrosis could be caused by the elongated turnover of collagen. Overall, we established a mouse model of radiation-induced vocal fold fibrosis using a simple protocol. Further investigations are warranted to elucidate the pathogenesis of irradiation-induced fibrosis in vocal folds. (c) 2022 Elsevier Inc. All rights reserved.