Yingzheng Zhao, Guangcui Xu, Haibin Li, Meiyu Chang, Cheng Xiong, Yingjun Tao, Yi Guan, Yuchun Li, Sanqiao Yao
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The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls.</p><p><strong>Results: </strong>The number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7.</p><p><strong>Conclusions: </strong>These findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. 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引用次数: 1
摘要
背景:矽肺的免疫调节异常与淋巴细胞氧化应激状态有关。抗氧化治疗对矽肺的潜在影响可能取决于外周血单核细胞(PBMCs)中核因子-红细胞2相关因子- 2 (NRF2)调控的抗氧化基因的变化。由于NRF2是一种氧化还原敏感转录因子，其在矽肺治疗中的可能作用及其机制有待进一步研究。方法:随机选取男性矽肺患者92例，健康男性志愿者87例。从矽肺患者和健康对照者的新鲜血液中分离出PBMCs。通过评估矽肺患者外周血淋巴细胞NRF2表达及NRF2依赖的抗氧化基因，研究其淋巴细胞氧化应激状态。利用RNA测序(RNA- seq)和生物信息学技术鉴定关键差异表达基因(deg)和信号通路。基因集富集分析用于鉴定矽肺患者和健康对照之间NRF2信号网络的差异。结果:矽肺患者单核细胞数量明显高于正常对照组。此外，利用定量聚合酶链反应证实了RNA-Seq结果，并揭示了nrf2调控的deg与矽肺患者外周血中谷胱甘肽代谢、转化生长因子-β和细胞外基质受体相互作用信号通路相关。PPI分析鉴定出前10个枢纽基因:SMAD2、MAPK3、THBS1、SMAD3、ITGB3、整合素α - v (ITGAV)、血管性血病因子(VWF)、BMP4、CD44和SMAD7。结论:这些发现表明NRF2信号调节淋巴细胞氧化应激状态，并可能参与人pbmc的纤维化反应。因此，NRF2可能作为一种新的预防和治疗矽肺的候选药物。
Genome-wide mRNA profiling identifies the NRF2-regulated lymphocyte oxidative stress status in patients with silicosis.
Background: The immunomodulatory abnormalities of silicosis are related to the lymphocyte oxidative stress state. The potential effect of antioxidant therapy on silicosis may depend on the variation in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant genes in peripheral blood mononuclear cells (PBMCs). As NRF2 is a redox-sensitive transcription factor, its possible roles and underlying mechanism in the treatment of silicosis need to be clarified.
Methods: Ninety-two male patients with silicosis and 87 male healthy volunteers were randomly selected. PBMCs were isolated from fresh blood from patients with silicosis and healthy controls. The lymphocyte oxidative stress state was investigated by evaluating NRF2 expression and NRF2-dependent antioxidative genes in PBMCs from patients with silicosis. Key differentially expressed genes (DEGs) and signaling pathways were identified utilizing RNA sequencing (RNA-Seq) and bioinformatics technology. Gene set enrichment analysis was used to identify the differences in NRF2 signaling networks between patients with silicosis and healthy controls.
Results: The number of monocytes was significantly higher in patients with silicosis than that of healthy controls. Furthermore, RNA-Seq findings were confirmed using quantitative polymerase chain reaction and revealed that NRF2-regulated DEGs were associated with glutathione metabolism, transforming growth factor-β, and the extracellular matrix receptor interaction signaling pathway in PBMCs from patients with silicosis. The top 10 hub genes were identified by PPI analysis: SMAD2, MAPK3, THBS1, SMAD3, ITGB3, integrin alpha-V (ITGAV), von Willebrand factor (VWF), BMP4, CD44, and SMAD7.
Conclusions: These findings suggest that NRF2 signaling regulates the lymphocyte oxidative stress state and may contribute to fibrogenic responses in human PBMCs. Therefore, NRF2 might serve as a novel preventive and therapeutic candidate for silicosis.
期刊介绍：
Aimed at clinicians and researchers, the Journal of Occupational Medicine and Toxicology is a multi-disciplinary, open access journal which publishes original research on the clinical and scientific aspects of occupational and environmental health.
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