Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis
Thyroid hormone (TH) and it most active form triiodothyronine (T3) are crucial in promoting mitochondrial biogenesis and maintaining cellular homeostasis during the stress response, but their role in paraquat (PQ)-induced pulmonary fibrosis isunclear. The aim of this study was to examine whether the...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325000491 |
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| author | Wenbo Chen Zhengguang Geng Haixia Luo Zhaoyuan Huang Yufen Yang Xun Luo Bao Fu Zhi Liu Xiaoyun Fu |
| author_facet | Wenbo Chen Zhengguang Geng Haixia Luo Zhaoyuan Huang Yufen Yang Xun Luo Bao Fu Zhi Liu Xiaoyun Fu |
| author_sort | Wenbo Chen |
| collection | DOAJ |
| description | Thyroid hormone (TH) and it most active form triiodothyronine (T3) are crucial in promoting mitochondrial biogenesis and maintaining cellular homeostasis during the stress response, but their role in paraquat (PQ)-induced pulmonary fibrosis isunclear. The aim of this study was to examine whether there was a deficiency of TH in mouse lung tissue after PQ administration, and to explore the effect of T3, and potential mechanisms of action, in alleviation of PQ-induced pulmonary fibrosis. We found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in the lungs of patients with pulmonary fibrosis than in controls. The expression of DIO2 in lung tissue of PQ injured mice was significantly increased compared to controls (P < 0.001), while the serum T3 level was significantly reduced, compared to the control group (P < 0.001). T3 nebulization significantly improved PQ-induced pulmonary fibrosis in mice, possibly by activating thyroid hormone receptor beta (THRβ). T3 and sobetirome, a specific THRβ agonist significantly upregulated peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC1α) expression, and NH-3 (an antagonist of the thyroid hormone receptor), a THRβ-specific antagonist, significantly inhibited (P < 0.0001) the beneficial effects of T3 on the PQ-induced mitochondrial apoptotic pathway in an epithelial cell line, in vitro. T3 via the THRβ / PGC1α pathway protected against PQ induced pulmonary fibrosis, furnishing a scientific basis for further research on T3 and this pathway could offer a potential novel therapeutic strategy for treating PQ poisoning in humans. |
| format | Article |
| id | doaj-art-4abd4f6a92834a06925408f1952c71de |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-4abd4f6a92834a06925408f1952c71de2025-01-23T05:26:12ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117713Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosisWenbo Chen0Zhengguang Geng1Haixia Luo2Zhaoyuan Huang3Yufen Yang4Xun Luo5Bao Fu6Zhi Liu7Xiaoyun Fu8Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China; Department of Emergency, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, China; Department of Critical Care Medicine, Kweichow Moutai Hospital, Renhuai, Guizhou 564500, ChinaDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaThe First Clinical Institute, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaSchool of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaSchool of Public Health, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaDepartment of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, ChinaDepartment of Emergency, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China; Corresponding author.Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, China; Corresponding author at: Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China.Thyroid hormone (TH) and it most active form triiodothyronine (T3) are crucial in promoting mitochondrial biogenesis and maintaining cellular homeostasis during the stress response, but their role in paraquat (PQ)-induced pulmonary fibrosis isunclear. The aim of this study was to examine whether there was a deficiency of TH in mouse lung tissue after PQ administration, and to explore the effect of T3, and potential mechanisms of action, in alleviation of PQ-induced pulmonary fibrosis. We found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in the lungs of patients with pulmonary fibrosis than in controls. The expression of DIO2 in lung tissue of PQ injured mice was significantly increased compared to controls (P < 0.001), while the serum T3 level was significantly reduced, compared to the control group (P < 0.001). T3 nebulization significantly improved PQ-induced pulmonary fibrosis in mice, possibly by activating thyroid hormone receptor beta (THRβ). T3 and sobetirome, a specific THRβ agonist significantly upregulated peroxlsome proliferator-activated receptor-γ coactlvator-1α (PGC1α) expression, and NH-3 (an antagonist of the thyroid hormone receptor), a THRβ-specific antagonist, significantly inhibited (P < 0.0001) the beneficial effects of T3 on the PQ-induced mitochondrial apoptotic pathway in an epithelial cell line, in vitro. T3 via the THRβ / PGC1α pathway protected against PQ induced pulmonary fibrosis, furnishing a scientific basis for further research on T3 and this pathway could offer a potential novel therapeutic strategy for treating PQ poisoning in humans.http://www.sciencedirect.com/science/article/pii/S0147651325000491Thyroid hormoneTriiodothyronineFibrosisParaquatPGC1α |
| spellingShingle | Wenbo Chen Zhengguang Geng Haixia Luo Zhaoyuan Huang Yufen Yang Xun Luo Bao Fu Zhi Liu Xiaoyun Fu Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis Ecotoxicology and Environmental Safety Thyroid hormone Triiodothyronine Fibrosis Paraquat PGC1α |
| title | Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis |
| title_full | Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis |
| title_fullStr | Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis |
| title_full_unstemmed | Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis |
| title_short | Triiodothyronine activates THRβ to promote PGC1α expression alleviating PQ-induced pulmonary fibrosis |
| title_sort | triiodothyronine activates thrβ to promote pgc1α expression alleviating pq induced pulmonary fibrosis |
| topic | Thyroid hormone Triiodothyronine Fibrosis Paraquat PGC1α |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325000491 |
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