2. Academic Validation
  3. 2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages

2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages

  • Ecotoxicol Environ Saf. 2023 Nov 30:269:115767. doi: 10.1016/j.ecoenv.2023.115767.
Yuting Lu 1,  Min Mu 2,  Xiaotian RenChen 1,  Wenyang Wang 3,  Yingrui Zhu 1,  Meiping Zhong 1,  Yuerong Jiang 1,  Xinrong Tao 4
Affiliations

Affiliations

  • 1 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, China.
  • 2 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, 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. Electronic address: candymu@126.com.
  • 3 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, China; Anhui Institute of Occupational Safety and Health, Anhui University of Science and Technology, China.
  • 4 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, 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.
PMID: 38039851 DOI: 10.1016/j.ecoenv.2023.115767
Abstract

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.

Keywords

2-DG; Alveolar macrophages; HIF-1α; Inflammation; Silicosis.

Figures
Products