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.

中文翻译：

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基于单细胞转录组测序的分析：探讨糖蛋白NMB对矽肺上皮细胞的调节机制

长期接触二氧化硅可导致矽肺，这是世界范围内最严重的职业性肺病之一，目前尚缺乏有效的治疗药物和工具。上皮间质转化在多种疾病中发挥重要作用；然而，有关矽肺模型具体机制的数据很少。我们通过单细胞转录组测序阐明了肺纤维化的发病机制，并构建了实验性矽肺小鼠模型，从单细胞水平探讨影响上皮间质转化的具体分子机制。值得注意的是，随着矽肺的进展，糖蛋白非转移性黑色素瘤蛋白B（GPNMB）对肺泡II型上皮细胞产生持续的放大效应，通过加速细胞增殖和迁移以及增加间质标志物来诱导上皮-间质转化，最终导致持久的矽肺病。肺部病理改变。GPNMB 通过释放细胞外囊泡加速矽肺，参与远处肺上皮细胞的上皮-间质转化。这些囊泡参与细胞外基质组成和胶原结构的异常变化。我们的结果表明 GPNMB 是预防纤维化的潜在靶点。