Single-cell transcriptome sequencing-based analysis: probing the mechanisms of glycoprotein NMB regulation of epithelial cells involved in silicosis.
Single-cell transcriptome sequencing-based analysis: probing the mechanisms of glycoprotein NMB regulation of epithelial cells involved in silicosis.
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DOI：
10.1186/s12989-023-00543-9
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发表时间：
2023-07-19
影响因子：
10
通讯作者：
中科院分区：
文献类型：
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长期接触二氧化硅可导致矽肺病，这是世界上最严重的职业性肺病之一，缺乏有效的治疗药物和工具。上皮间充质转化在多种疾病中起重要作用；然而，关于矽肺模型的具体机制的数据很少。我们通过单细胞转录组测序阐明肺纤维化的发病机制，构建实验性矽肺小鼠模型，探索单细胞水平上影响上皮间质转化的特定分子机制。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型上皮细胞发挥持续的扩增作用，通过加速细胞增殖和迁移，增加间质标志物，诱导上皮向间质转化，最终导致肺部持续病理改变。GPNMB通过释放细胞外囊泡加速矽肺，参与远端肺上皮细胞的上皮-间质转化。这些囊泡与细胞外基质和胶原结构组成的异常变化有关。我们的研究结果表明GPNMB是预防纤维化的潜在靶点。在线版本包含补充材料，可在10.1186/s12989-023-00543-9获得。
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. The online version contains supplementary material available at 10.1186/s12989-023-00543-9.
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影响因子：
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