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Updated: Jul 23, 2025
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
Single-cell transcriptome sequencing-based analysis: probing the mechanisms of glycoprotein NMB regulation of
Shaoqi Yang1,2, Yuheng Sun1,2, Min Long3
1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Physiology, School of Medicine, Zhongda Hospital, Southeast University, 87 Dingjiaqiao Rd, Nanjing, Jiangsu, 210009, China.
Abstract:
Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs and tools. Epithelial mesenchymal transition plays an important role in several diseases; however, data on the specific mechanisms in silicosis models are scarce. We elucidated the pathogenesis of pulmonary fibrosis via single-cell transcriptome sequencing and constructed an experimental silicosis mouse model to explore the specific molecular mechanisms affecting epithelial mesenchymal transition at the single-cell level. Notably, as silicosis progressed, glycoprotein non-metastatic melanoma protein B (GPNMB) exerted a sustained amplification effect on alveolar type II epithelial cells, inducing epithelial-to-mesenchymal transition by accelerating cell proliferation and migration and increasing mesenchymal markers, ultimately leading to persistent pulmonary pathological changes. GPNMB participates in the epithelial-mesenchymal transition in distant lung epithelial cells by releasing extracellular vesicles to accelerate silicosis. These vesicles are involved in abnormal changes in the composition of the extracellular matrix and collagen structure. Our results suggest that GPNMB is a potential target for fibrosis prevention.
Insights
Glycoprotein non-metastatic melanoma protein B (GPNMB) drives silicosis progression by promoting epithelial-to-mesenchymal transition in lung cells. Targeting GPNMB may offer a new strategy for preventing pulmonary fibrosis caused by silica exposure.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Toxicology
Background:
- Silicosis is a severe occupational lung disease with limited treatment options.
- Epithelial-mesenchymal transition (EMT) is implicated in disease but its role in silicosis is not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms of pulmonary fibrosis in silicosis.
- To explore the role of EMT in silicosis pathogenesis at the single-cell level.
Main Methods:
- Construction of a mouse model for experimental silicosis.
- Single-cell transcriptome sequencing to analyze cellular changes.
- Investigation of glycoprotein non-metastatic melanoma protein B (GPNMB) function.
Main Results:
- GPNMB promotes EMT in alveolar type II epithelial cells, accelerating proliferation and migration.
- GPNMB-containing extracellular vesicles contribute to silicosis progression and alter extracellular matrix.
- Sustained GPNMB activity leads to persistent pulmonary pathological changes.
Conclusions:
- GPNMB plays a critical role in driving EMT and fibrosis in silicosis.
- GPNMB is a potential therapeutic target for preventing silica-induced pulmonary fibrosis.
