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低剂量电离辐射:通过激活Wnt/β-连环蛋白信号通路对晶状体上皮细胞增殖和迁移的影响

Low-dose ionizing radiation: Effects on the proliferation and migration of lens epithelial cells via activation of the Wnt/β-catenin pathway.

作者信息

Wang Ping, Li Yu-Wen, Lu Xue, Liu Ya, Tian Xue-Lei, Gao Ling, Liu Qing-Jie, Fan Li, Tian Mei

机构信息

China CDC Key Laboratory of Radiation Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, PR China.

National Center for Occupational Safety and Health, NHC, Beijing 102308, PR China.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2023 May-Jun;888:503637. doi: 10.1016/j.mrgentox.2023.503637. Epub 2023 Apr 20.

DOI:10.1016/j.mrgentox.2023.503637
PMID:37188435
Abstract

Eye lens opacification (cataract) induced by ionizing radiation is an important concern for radiation protection. Human lens epithelial cells (HLE-B3) were irradiated with γ-rays and radiation effects, including cell proliferation, cell migration, cell cycle distribution, and other changes related to the β-catenin pathway, were determined after 8-72 h and 7 d. In an in vivo model, mice were irradiated; DNA damage (γH2AX foci) in the cell nucleus of the anterior capsule of the lens was detected within 1 h, and radiation effects on the anterior and posterior lens capsules were observed after 3 months. Low-dose ionizing radiation promoted cell proliferation and migration. The expression levels of β-catenin, cyclin D1, and c-Myc were significantly increased in HLE-B3 cells after irradiation and β-catenin was translocated into the cell nucleus (activation of the Wnt/β-catenin pathway). In C57BL/6 J mouse lens, even a very low irradiation dose (0.05 Gy) induced the formation of γH2AX foci, 1 h after irradiation. At 3 months, migratory cells were found in the posterior capsule; expression of β-catenin was increased and it was clustered at the nucleus in the epithelial cells of the lens anterior capsule. The Wnt/β-catenin signaling pathway may an important role in promoting abnormal proliferation and migration of lens epithelial cells after low-dose irradiation.

摘要

电离辐射诱导的晶状体混浊(白内障)是辐射防护的一个重要关注点。用γ射线照射人晶状体上皮细胞(HLE-B3),并在8 - 72小时和7天后测定辐射效应,包括细胞增殖、细胞迁移、细胞周期分布以及与β-连环蛋白途径相关的其他变化。在体内模型中,对小鼠进行照射;照射后1小时内检测晶状体前囊细胞核中的DNA损伤(γH2AX焦点),并在3个月后观察对晶状体前、后囊的辐射效应。低剂量电离辐射促进细胞增殖和迁移。照射后HLE-B3细胞中β-连环蛋白、细胞周期蛋白D1和c-Myc的表达水平显著增加,并且β-连环蛋白易位至细胞核(Wnt/β-连环蛋白途径激活)。在C57BL/6 J小鼠晶状体中,即使是非常低的照射剂量(0.05 Gy)在照射后1小时也会诱导γH2AX焦点的形成。3个月时,在后囊中发现迁移细胞;β-连环蛋白的表达增加,并且在晶状体前囊上皮细胞的细胞核中聚集。Wnt/β-连环蛋白信号通路可能在低剂量照射后促进晶状体上皮细胞异常增殖和迁移中起重要作用。

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