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DOI: 10.5999/aps.2018.00101
Development of an easy-to-handle murine model for the characterization of radiation-induced gross and molecular changes in skin
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (grant no. 2013R1A1A1009764 to Lee DW).
Background Radiation-induced skin injury is a dose-limiting complication of radiotherapy. To investigate this problem and to develop a framework for making decisions on treatment and dose prescription, a murine model of radiation-induced skin injury was developed.
Methods The dorsal skin of the mice was isolated, and irradiation was applied at single doses of 15, 30, and 50 Gy. The mice were followed for 12 weeks with serial photography and laser Doppler analysis. Sequential skin biopsy samples were obtained and subjected to a histological analysis, immunostaining against transforming growth factor beta (TGF-β), and Western blotting with Wnt-3 and β-catenin. Increases in the levels of TGF-β, Wnt, and β-catenin were detected after irradiation.
Results All tested radiation doses caused progressive dermal thickening and fibrosis. The cause of this process, however, may not be radiation alone, as the natural course of wound healing may elicit a similar response. The latent appearance of molecular and histological markers that induce fibrosis in the 15 Gy group without causing apparent gross skin injuries indicates that 15 Gy is an appropriate dose for characterizing the effects of chronic irradiation alone. Thus, this model best mimics the patterns of injury that occur in human subjects.
Conclusions This animal model can be used to elucidate the gross and molecular changes that occur in radiation-induced skin injury and provides an effective platform for studying this adverse effect without complicating the process of wound healing.
Supplemental Fig. S1.
- Supplementary material
Gross photographs and serial blood flow
(A) Representative photographs of the skin at weeks 2, 4, 6, 8, and 10 after a single radiation treatment with various doses. (B) Serial analysis of skin blood flow measured using laser Doppler after irradiation (perfusion units). *P<0.05 vs. the 40 and 50 Gy group, n=3. (https://doi.org/10.5999/aps.2018.00101).
Publication History
Received: 26 January 2018
Accepted: 03 July 2018
Article published online:
03 April 2022
© 2018. The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonCommercial License, permitting unrestricted noncommercial use, distribution, and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes. (https://creativecommons.org/licenses/by-nc/4.0/)
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