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Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling

Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated...

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Autores principales: Kim, Hyuna, Yoo, Woong-Sun, Jung, Jung Hwa, Jeong, Bae Kwon, Woo, Seung Hoon, Kim, Jin Hyun, Kim, Seong Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888725/
https://www.ncbi.nlm.nih.gov/pubmed/31766286
http://dx.doi.org/10.3390/ijms20225691
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author Kim, Hyuna
Yoo, Woong-Sun
Jung, Jung Hwa
Jeong, Bae Kwon
Woo, Seung Hoon
Kim, Jin Hyun
Kim, Seong Jae
author_facet Kim, Hyuna
Yoo, Woong-Sun
Jung, Jung Hwa
Jeong, Bae Kwon
Woo, Seung Hoon
Kim, Jin Hyun
Kim, Seong Jae
author_sort Kim, Hyuna
collection PubMed
description Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation–induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.
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spelling pubmed-68887252019-12-09 Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling Kim, Hyuna Yoo, Woong-Sun Jung, Jung Hwa Jeong, Bae Kwon Woo, Seung Hoon Kim, Jin Hyun Kim, Seong Jae Int J Mol Sci Article Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient’s daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation–induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome. MDPI 2019-11-13 /pmc/articles/PMC6888725/ /pubmed/31766286 http://dx.doi.org/10.3390/ijms20225691 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Hyuna
Yoo, Woong-Sun
Jung, Jung Hwa
Jeong, Bae Kwon
Woo, Seung Hoon
Kim, Jin Hyun
Kim, Seong Jae
Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title_full Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title_fullStr Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title_full_unstemmed Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title_short Alpha-Lipoic Acid Ameliorates Radiation-Induced Lacrimal Gland Injury through NFAT5-Dependent Signaling
title_sort alpha-lipoic acid ameliorates radiation-induced lacrimal gland injury through nfat5-dependent signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888725/
https://www.ncbi.nlm.nih.gov/pubmed/31766286
http://dx.doi.org/10.3390/ijms20225691
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