2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages
Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S014765132301271X |
| _version_ | 1797435822049329152 |
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| author | Yuting Lu Min Mu Xiaotian RenChen Wenyang Wang Yingrui Zhu Meiping Zhong Yuerong Jiang Xinrong Tao |
| author_facet | Yuting Lu Min Mu Xiaotian RenChen Wenyang Wang Yingrui Zhu Meiping Zhong Yuerong Jiang Xinrong Tao |
| author_sort | Yuting Lu |
| collection | DOAJ |
| description | Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1β (IL-1β) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1β, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis. |
| first_indexed | 2024-03-09T10:53:44Z |
| format | Article |
| id | doaj.art-d0710ba9f7a24cd6b74c7bfb69172852 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-09T10:53:44Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-d0710ba9f7a24cd6b74c7bfb691728522023-12-01T05:00:39ZengElsevierEcotoxicology and Environmental Safety0147-65132024-01-012691157672-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophagesYuting Lu0Min Mu1Xiaotian RenChen2Wenyang Wang3Yingrui Zhu4Meiping Zhong5Yuerong Jiang6Xinrong Tao7School of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, China; Anhui Institute of Occupational Safety and Health, Anhui University of Science and Technology, China; Joint Research Center of Occupational Medicine and Health, Institute of Grand Health, Hefei Comprehensive National Science Center, Anhui University of Science and Technology, China; Correspondence to: Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education, Anhui University of Science and Technology, 168 taifeng Road, Huainan City, Anhui Province 232001, China.School of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, China; Anhui Institute of Occupational Safety and Health, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, ChinaSchool of Public Health, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Prevention and Control, Occupational Safety and Health, Ministry of Education, Anhui University of Science and Technology, China; Anhui Institute of Occupational Safety and Health, Anhui University of Science and Technology, China; Joint Research Center of Occupational Medicine and Health, Institute of Grand Health, Hefei Comprehensive National Science Center, Anhui University of Science and Technology, ChinaInhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1β (IL-1β) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1β, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.http://www.sciencedirect.com/science/article/pii/S014765132301271XAlveolar macrophagesHIF-1αInflammationSilicosis2-DG |
| spellingShingle | Yuting Lu Min Mu Xiaotian RenChen Wenyang Wang Yingrui Zhu Meiping Zhong Yuerong Jiang Xinrong Tao 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages Ecotoxicology and Environmental Safety Alveolar macrophages HIF-1α Inflammation Silicosis 2-DG |
| title | 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages |
| title_full | 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages |
| title_fullStr | 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages |
| title_full_unstemmed | 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages |
| title_short | 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages |
| title_sort | 2 deoxy d glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia inducible factor 1α in alveolar macrophages |
| topic | Alveolar macrophages HIF-1α Inflammation Silicosis 2-DG |
| url | http://www.sciencedirect.com/science/article/pii/S014765132301271X |
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