Particle and Fibre Toxicology (Jul 2023)

Single-cell transcriptome sequencing–based analysis: probing the mechanisms of glycoprotein NMB regulation of epithelial cells involved in silicosis

  • Shaoqi Yang,
  • Yuheng Sun,
  • Min Long,
  • Xinbei Zhou,
  • Mengqin Yuan,
  • Liliang Yang,
  • Wei Luo,
  • Yusi Cheng,
  • Xinxin Zhang,
  • Wei Jiang,
  • Jie Chao

DOI
https://doi.org/10.1186/s12989-023-00543-9
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 17

Abstract

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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.

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