Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.
Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.
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DOI：
10.1186/1748-717x-3-40
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发表时间：
2008-11-24
影响因子：
3.6
通讯作者：
Kim, Jae Ho
中科院分区：
文献类型：
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作者：
Kumar, Sanath;Kolozsvary, Andrew;Kohl, Robert;Lu, Mei;Brown, Stephen;Kim, Jae Ho
由于纤维化风险增加，患有胶原血管疾病（CVD）（如硬皮病）的癌症患者通常忌讳放射治疗。紧致皮肤（TSK）小鼠的皮肤在某些方面模仿硬皮病患者的皮肤。TSK小鼠的皮肤辐射反应此前未见报道。如果TSK小鼠被证明具有辐射敏感皮肤，它们可能被证明是研究皮肤辐射损伤、保护、缓解和治疗机制的有用模型。TSK和亲代对照C57BL/6小鼠的后肢受到的辐射暴露足以造成大致相同水平的急性损伤。终点包括使用非线性、半定量量表评分的皮肤损伤和通过测量被动腿伸展评估的组织纤维化。此外，每月检测皮肤组织中TGF-β1细胞因子水平。与我们的预期相反，TSK小鼠比亲代对照小鼠对辐射的抵抗力更强（即20%）。虽然两种小鼠的急性皮肤反应相似，但TSK小鼠的辐射损伤随着时间的推移而持续减轻，与C57BL/6小鼠相比，辐射后几个月皮肤损伤和腿部收缩明显减少（p < 0.05）。与预期的转化生长因子β -1 （TGF-β1）与晚期组织损伤的相关性一致，C57BL/6小鼠皮肤中TGF-β1水平在所有时间点均显著高于TSK小鼠（p < 0.05）。不推荐TSK小鼠作为涉及辐射损伤的硬皮病模型。在TSK小鼠中观察到的减少辐射损伤的遗传和分子基础值得进一步研究，特别是确定能够减少辐射损伤后组织纤维化的机制。
Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. The tight skin (TSK) mouse has skin which, in some respects, mimics that of patients with scleroderma. The skin radiation response of TSK mice has not been previously reported. If TSK mice are shown to have radiation sensitive skin, they may prove to be a useful model to examine the mechanisms underlying skin radiation injury, protection, mitigation and treatment. The hind limbs of TSK and parental control C57BL/6 mice received a radiation exposure sufficient to cause approximately the same level of acute injury. Endpoints included skin damage scored using a non-linear, semi-quantitative scale and tissue fibrosis assessed by measuring passive leg extension. In addition, TGF-β1 cytokine levels were measured monthly in skin tissue. Contrary to our expectations, TSK mice were more resistant (i.e. 20%) to radiation than parental control mice. Although acute skin reactions were similar in both mouse strains, radiation injury in TSK mice continued to decrease with time such that several months after radiation there was significantly less skin damage and leg contraction compared to C57BL/6 mice (p < 0.05). Consistent with the expected association of transforming growth factor beta-1 (TGF-β1) with late tissue injury, levels of the cytokine were significantly higher in the skin of the C57BL/6 mouse compared to TSK mouse at all time points (p < 0.05). TSK mice are not recommended as a model of scleroderma involving radiation injury. The genetic and molecular basis for reduced radiation injury observed in TSK mice warrants further investigation particularly to identify mechanisms capable of reducing tissue fibrosis after radiation injury.