Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice

Abstract Background Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified. Currently, the only effective treatment for RAD is rehabilitation....

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Main Authors: Shuntaro Soejima, Chia-Hsien Wu, Haruna Matsuse, Mariko Terakado, Shinji Okano, Tsuyoshi Inoue, Yoshihiko Kumai
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Laboratory Animal Research
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Online Access:https://doi.org/10.1186/s42826-024-00199-2
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author Shuntaro Soejima
Chia-Hsien Wu
Haruna Matsuse
Mariko Terakado
Shinji Okano
Tsuyoshi Inoue
Yoshihiko Kumai
author_facet Shuntaro Soejima
Chia-Hsien Wu
Haruna Matsuse
Mariko Terakado
Shinji Okano
Tsuyoshi Inoue
Yoshihiko Kumai
author_sort Shuntaro Soejima
collection DOAJ
description Abstract Background Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified. Currently, the only effective treatment for RAD is rehabilitation. Additionally, there are few available animal models of RAD, necessitating the development of new models to establish and evaluate RAD treatments. We hypothesize that radiation-induced neck muscle fibrosis could be one of the causes of RAD due to impairment of laryngeal elevation. Therefore, in this study, we focused on the changes in inflammation and fibrosis of the strap muscles (Sternohyoid, Sternothyroid, and Thyrohyoid muscles) after a single-dose irradiation. This research aims to provide a reference animal model for future studies on RAD. Results Compared to control mice, those treated with 20-Gy, but not 6.7-Gy, irradiation had significantly increased tumor necrosis factor-α (TNF-α) (p < 0.01) and α-smooth muscle actin (αSMA) (p < 0.05) expression at 10 days and significantly increased expression levels of motif chemokine ligand-2 (CCL2), α-SMA, tumor growth factor-β1 (TGF-β1), type1 collagen, and interleukin-1β (IL-1β) (p < 0.05) in the muscles at 1 month by real-time PCR analysis. The results of immunohistochemistry showed that the deposition of type 1 collagen gradually increased in extracellular space after radiation exposure, and the positive area was significantly increased at 3 months compared to non-irradiated control. Conclusions A single dose of 20-Gy irradiation induced significant inflammation and fibrosis in the strap muscles of mice at 1 month, with immunohistochemical changes becoming evident at 3 months. This cervical irradiation-induced fibrosis model holds potential for establishing an animal model for RAD in future studies. Level of evidence N/A.
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spelling doaj-art-1d49620bb6dc48daa3394421e7e1f0372025-02-09T12:09:14ZengBMCLaboratory Animal Research2233-76602024-04-014011910.1186/s42826-024-00199-2Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in miceShuntaro Soejima0Chia-Hsien Wu1Haruna Matsuse2Mariko Terakado3Shinji Okano4Tsuyoshi Inoue5Yoshihiko Kumai6Department of Otolaryngology Head and Neck Surgery Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Otolaryngology Head and Neck Surgery Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Otolaryngology Head and Neck Surgery Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki UniversityDepartment of Otolaryngology Head and Neck Surgery Graduate School of Biomedical Sciences, Nagasaki UniversityAbstract Background Although radiotherapy is commonly used to treat head and neck cancer, it may lead to radiation-associated dysphagia (RAD). There are various causes of RAD, however, the mechanism has not yet been fully identified. Currently, the only effective treatment for RAD is rehabilitation. Additionally, there are few available animal models of RAD, necessitating the development of new models to establish and evaluate RAD treatments. We hypothesize that radiation-induced neck muscle fibrosis could be one of the causes of RAD due to impairment of laryngeal elevation. Therefore, in this study, we focused on the changes in inflammation and fibrosis of the strap muscles (Sternohyoid, Sternothyroid, and Thyrohyoid muscles) after a single-dose irradiation. This research aims to provide a reference animal model for future studies on RAD. Results Compared to control mice, those treated with 20-Gy, but not 6.7-Gy, irradiation had significantly increased tumor necrosis factor-α (TNF-α) (p < 0.01) and α-smooth muscle actin (αSMA) (p < 0.05) expression at 10 days and significantly increased expression levels of motif chemokine ligand-2 (CCL2), α-SMA, tumor growth factor-β1 (TGF-β1), type1 collagen, and interleukin-1β (IL-1β) (p < 0.05) in the muscles at 1 month by real-time PCR analysis. The results of immunohistochemistry showed that the deposition of type 1 collagen gradually increased in extracellular space after radiation exposure, and the positive area was significantly increased at 3 months compared to non-irradiated control. Conclusions A single dose of 20-Gy irradiation induced significant inflammation and fibrosis in the strap muscles of mice at 1 month, with immunohistochemical changes becoming evident at 3 months. This cervical irradiation-induced fibrosis model holds potential for establishing an animal model for RAD in future studies. Level of evidence N/A.https://doi.org/10.1186/s42826-024-00199-2Radiation-induced fibrosisRadiation-associated dysphagiaAnimal modelMouseStrap muscle
spellingShingle Shuntaro Soejima
Chia-Hsien Wu
Haruna Matsuse
Mariko Terakado
Shinji Okano
Tsuyoshi Inoue
Yoshihiko Kumai
Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
Laboratory Animal Research
Radiation-induced fibrosis
Radiation-associated dysphagia
Animal model
Mouse
Strap muscle
title Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
title_full Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
title_fullStr Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
title_full_unstemmed Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
title_short Swallowing-related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
title_sort swallowing related muscle inflammation and fibrosis induced by a single dose of radiation exposure in mice
topic Radiation-induced fibrosis
Radiation-associated dysphagia
Animal model
Mouse
Strap muscle
url https://doi.org/10.1186/s42826-024-00199-2
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