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12 October 2020 Activated Beta-Catenin Signaling Ameliorates Radiation-Induced Skin Injury by Suppressing Marvel D3 Expression
Jinming Cao, Li Zhong, Yang Feng, Kun Qian, Yuji Xiao, Gaoren Wang, Wenling Tu, Ling Yue, Qi Zhang, Hongying Yang, Yang Jiao, Wei Zhu, Jianping Cao
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Abstract

Radiation-induced skin injury remains a serious concern for cancer radiotherapy, radiation accidents and occupational exposure, and the damage mainly occurs due to apoptosis and reactive oxygen species (ROS) generation. There is currently no effective treatment for this disorder. The β-catenin signaling pathway is involved in the repair and regeneration of injured tissues. However, the role of the β-catenin signaling pathway in radiation-induced skin injury has not been reported. In this study, we demonstrated that the β-catenin signaling pathway was activated in response to radiation and that its activation by Wnt3a, a ligand-protein involved in the β-catenin signaling pathway, inhibited apoptosis and the production of ROS in irradiated human keratinocyte HaCaT cells and skin fibroblast WS1 cells. Additionally, Wnt3a promoted cell migration after irradiation. In a mouse model of full-thickness skin wounds combined with total-body irradiation, Wnt3a was shown to facilitate skin wound healing. The results from RNA-Seq revealed that 24 genes were upregulated and 154 were downregulated in Wnt3a-treated irradiated skin cells, and these dysregulated genes were mainly enriched in the tight junction pathway. Among them, Marvel D3 showed the most obvious difference. We further found that the activated β-catenin signaling pathway stimulated the phosphorylation of JNK by silencing Marvel D3. Treatment of irradiated cells with SP600125, a JNK inhibitor, augmented ROS production and impeded cell migration. Furthermore, treatment with Wnt3a or transfection with Marvel D3-specific siRNAs could reverse the above effects. Taken together, these findings illustrate that activated β-catenin signaling stimulates the activation of JNK by negatively regulating Marvel D3 to ameliorate radiation-induced skin injury.

©2021 by Radiation Research Society. All rights of reproduction in any form reserved.
Jinming Cao, Li Zhong, Yang Feng, Kun Qian, Yuji Xiao, Gaoren Wang, Wenling Tu, Ling Yue, Qi Zhang, Hongying Yang, Yang Jiao, Wei Zhu, and Jianping Cao "Activated Beta-Catenin Signaling Ameliorates Radiation-Induced Skin Injury by Suppressing Marvel D3 Expression," Radiation Research 195(2), 173-190, (12 October 2020). https://doi.org/10.1667/RADE-20-00050.1
Received: 21 February 2020; Accepted: 4 September 2020; Published: 12 October 2020
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