The research on the mechanism of GBP2 promoting the progression of silicosis by inducing macrophage polarization and epithelial cell transformation.
- Author:
Maoqian CHEN
1
;
Jing WU
2
;
Xuan LI
1
;
Jiawei ZHOU
1
;
Yafeng LIU
1
;
Jianqiang GUO
1
;
Anqi CHENG
1
;
Dong HU
3
Author Information
1. School of Medicine, Anhui University of Science and Technology, Huainan 232001, China.
2. School of Medicine, Anhui University of Science and Technology, Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan 232001, China. *Corresponding authors, E-mail: aust_jingwu@aust.edu.cn.
3. School of Medicine, Anhui University of Science and Technology, Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan 232001, China. *Corresponding authors, E-mail: dhu@aust.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Silicosis/genetics*;
Macrophages/cytology*;
Epithelial Cells/pathology*;
GTP-Binding Proteins/physiology*;
Epithelial-Mesenchymal Transition;
Disease Progression;
Cell Line;
Male
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(7):611-619
- CountryChina
- Language:Chinese
-
Abstract:
Objective This study aims to investigate the expression, phenotypic changes, and mechanisms of action of guanylate-binding protein 2 (GBP2) in the process of silica-induced pulmonary fibrosis. Methods The expression and localization of GBP2 in silicotic lung tissue were detected by immunohistochemical staining and immunofluorescence. An in vitro cell model was constructed, and methods such as Western blot and real-time quantitative reverse transcription polymerasechain reaction were utilized to investigate the function of GBP2 in different cell lines following silica stimulation. The mechanism of action of GBP2 in various cell lines was elucidated using Western blot analysis. Results GBP2 was highly expressed in the lung tissue of patients with silicosis. Immunohistochemical staining and immunofluorescence have revealed that GBP2 was localized in macrophages and epithelial cells. In vitro cell experiments demonstrated that silicon dioxide stimulated THP-1 cells to activate the c-Jun pathway through GBP2, promoting the secretion of inflammatory factors and facilitating the occurrence of M2 macrophage polarization. In epithelial cells, GBP2 promoted the occurrence of epithelial to mesenchymal transition (EMT) by upregulating Krueppel-like factor 8 (KLF8). Conclusion GBP2 not only activates c-Jun in macrophages to promote the production of inflammatory factors and the occurrence of M2 macrophage polarization, but also activates the transcription factor KLF8 in epithelial cells to induce EMT, collectively promoting the progression of silicosis.
