T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model
Chronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endo...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/1/30 |
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| author | Noriki Takahashi Ryunosuke Nakashima Aoi Nasu Megumi Hayashi Haruka Fujikawa Taisei Kawakami Yuka Eto Tomoki Kishimoto Ayami Fukuyama Choyo Ogasawara Keisuke Kawano Yukio Fujiwara Mary Ann Suico Hirofumi Kai Tsuyoshi Shuto |
| author_facet | Noriki Takahashi Ryunosuke Nakashima Aoi Nasu Megumi Hayashi Haruka Fujikawa Taisei Kawakami Yuka Eto Tomoki Kishimoto Ayami Fukuyama Choyo Ogasawara Keisuke Kawano Yukio Fujiwara Mary Ann Suico Hirofumi Kai Tsuyoshi Shuto |
| author_sort | Noriki Takahashi |
| collection | DOAJ |
| description | Chronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endotype classifications. In this study, we explore the potential therapeutic role of thyroid hormone (T<sub>3</sub>) by using mouse models: emphysema-dominant elastase-induced COPD and airway-dominant C57BL/6-βENaC-Tg to represent different types of the disease. Here, we showed that intratracheal T<sub>3</sub> treatment (40, 80 μg/kg, <i>i.t.</i>, every other day) resulted in significant improvements regarding emphysema and the enhancement of respiratory function in the elastase-induced COPD model. T<sub>3</sub>-dependent improvement is likely linked to the up-regulation of <i>Ppargc1a</i>, a master regulator of mitochondrial biogenesis, and <i>Gclm</i>, a factor associated with oxidative stress. Conversely, neither short- nor long-term T<sub>3</sub> treatments improved COPD pathology in the C57BL/6-βENaC-Tg mice. Because the up-regulation of extrathyroidal T<sub>3</sub>-producing enzyme <i>Dio2</i>, which is also considered a marker of T<sub>3</sub> requirement, was specifically observed in elastase-induced COPD lungs, these results demonstrate that exogenous T<sub>3</sub> supplementation may have therapeutic potential for acute but not chronic COPD exacerbation. Moreover, this study highlights the relevance of considering not only COPD phenotypes but also COPD endotypes (expression levels of <i>Ppargc1a</i> and/or <i>Dio2</i>) in the research and development of better treatment approaches for COPD. |
| first_indexed | 2024-03-08T11:07:06Z |
| format | Article |
| id | doaj.art-429d4f2c1e6347a3864b86644b249303 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T11:07:06Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-429d4f2c1e6347a3864b86644b2493032024-01-26T14:40:13ZengMDPI AGAntioxidants2076-39212023-12-011313010.3390/antiox13010030T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse ModelNoriki Takahashi0Ryunosuke Nakashima1Aoi Nasu2Megumi Hayashi3Haruka Fujikawa4Taisei Kawakami5Yuka Eto6Tomoki Kishimoto7Ayami Fukuyama8Choyo Ogasawara9Keisuke Kawano10Yukio Fujiwara11Mary Ann Suico12Hirofumi Kai13Tsuyoshi Shuto14Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto Chuo-ku, Kumamoto 860-8556, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanDepartment of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, JapanChronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endotype classifications. In this study, we explore the potential therapeutic role of thyroid hormone (T<sub>3</sub>) by using mouse models: emphysema-dominant elastase-induced COPD and airway-dominant C57BL/6-βENaC-Tg to represent different types of the disease. Here, we showed that intratracheal T<sub>3</sub> treatment (40, 80 μg/kg, <i>i.t.</i>, every other day) resulted in significant improvements regarding emphysema and the enhancement of respiratory function in the elastase-induced COPD model. T<sub>3</sub>-dependent improvement is likely linked to the up-regulation of <i>Ppargc1a</i>, a master regulator of mitochondrial biogenesis, and <i>Gclm</i>, a factor associated with oxidative stress. Conversely, neither short- nor long-term T<sub>3</sub> treatments improved COPD pathology in the C57BL/6-βENaC-Tg mice. Because the up-regulation of extrathyroidal T<sub>3</sub>-producing enzyme <i>Dio2</i>, which is also considered a marker of T<sub>3</sub> requirement, was specifically observed in elastase-induced COPD lungs, these results demonstrate that exogenous T<sub>3</sub> supplementation may have therapeutic potential for acute but not chronic COPD exacerbation. Moreover, this study highlights the relevance of considering not only COPD phenotypes but also COPD endotypes (expression levels of <i>Ppargc1a</i> and/or <i>Dio2</i>) in the research and development of better treatment approaches for COPD.https://www.mdpi.com/2076-3921/13/1/30thyroid hormone (T<sub>3</sub>)chronic obstructive pulmonary disease (COPD)disease type classificationmitochondrial functionantioxidant effectpulmo-modulatory factors |
| spellingShingle | Noriki Takahashi Ryunosuke Nakashima Aoi Nasu Megumi Hayashi Haruka Fujikawa Taisei Kawakami Yuka Eto Tomoki Kishimoto Ayami Fukuyama Choyo Ogasawara Keisuke Kawano Yukio Fujiwara Mary Ann Suico Hirofumi Kai Tsuyoshi Shuto T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model Antioxidants thyroid hormone (T<sub>3</sub>) chronic obstructive pulmonary disease (COPD) disease type classification mitochondrial function antioxidant effect pulmo-modulatory factors |
| title | T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model |
| title_full | T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model |
| title_fullStr | T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model |
| title_full_unstemmed | T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model |
| title_short | T<sub>3</sub> Intratracheal Therapy Alleviates Pulmonary Pathology in an Elastase-Induced Emphysema-Dominant COPD Mouse Model |
| title_sort | t sub 3 sub intratracheal therapy alleviates pulmonary pathology in an elastase induced emphysema dominant copd mouse model |
| topic | thyroid hormone (T<sub>3</sub>) chronic obstructive pulmonary disease (COPD) disease type classification mitochondrial function antioxidant effect pulmo-modulatory factors |
| url | https://www.mdpi.com/2076-3921/13/1/30 |
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