Comparative RNA-Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model
Comparative RNA-Seq transcriptome analysis on silica induced pulmonary inflammation and fibrosis in mice silicosis model
复制标题
二氧化硅诱导小鼠矽肺模型肺部炎症和纤维化的比较 RNA-Seq 转录组分析
DOI：
10.1002/jat.3587
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发表时间：
2018-05-01
影响因子：
3.3
通讯作者：
Xiong, Jingyuan
中科院分区：
文献类型：
--
作者：
Chen, Jiayi;Yao, Yuqin;Xiong, Jingyuan
由于日益严重的空气污染和执行不力的职业安全法规，矽肺是发展中国家长期存在的公共卫生问题。吸入二氧化硅会引发细胞毒性、氧化应激、肺部炎症，最终导致矽肺。目前对矽肺的发病机制和发病机制的认识有限，一旦发生矽肺，临床上没有有效的治疗方法。进行了许多研究以调查二氧化硅诱导的肺细胞中的替代基因表达。然而，需要在矽肺动物模型中进行转录组分析。本研究使用比较RNA-Seq评估矽肺小鼠中的转录改变。采用硅胶混悬液灌胃法建立小鼠矽肺模型，并进行组织学检查。高通量测序和差异表达基因分析显示，在矽肺模型中有749个上调基因和70个下调基因。与免疫细胞相互作用、免疫细胞应答和炎症相关的基因显著富集。细胞因子-细胞因子受体相互作用和下游JAK-STAT信号通路是最显著富集的KEGG通路。逆转录-聚合酶链反应分析和免疫组织化学进行进一步验证的代表性基因的差异表达模式。本研究的结果为阐明矽尘致肺炎症和纤维化的分子机制提供了依据，为矽尘病的防治提供了理论依据。高通量RNA-Seq和DGE分析显示749个上调基因和70个下调基因。与免疫细胞相互作用、免疫细胞应答和炎症相关的基因显著富集。细胞因子-细胞因子受体相互作用和下游JAK-STAT信号通路显著富集KEGG通路。本研究结果为阐明矽尘致肺部炎症和纤维化的分子机制提供了依据，为矽尘病的防治提供了理论依据。
Silicosis is a long-established public health issue in developing countries due to increasingly serious air pollution and poorly implemented occupational safety regulation. Inhalation of silica triggers cytotoxicity, oxidative stress, pulmonary inflammation and eventually silicosis. Current understanding in the pathogenesis and mechanism of silicosis is limited, and no effective cure is clinically available once silicosis is developed. A number of studies were conducted to investigate silica-induced alternate gene expressions in pulmonary cells. However, transcriptome analysis in a silicosis animal model is needed. This study was performed to evaluate the transcriptional alternations in silicotic mice using comparative RNA-Seq. A silicosis mice model was established by intratracheal instillation of silica suspensions, and validated by histological examinations. High-throughput sequencing and differential gene expression analysis revealed 749 upregulated genes and 70 downregulated genes in the silicosis model. Genes related to immune cell interactions, immune cell responses and inflammation were significantly enriched. Cytokine-cytokine receptor interaction and downstream JAK-STAT signaling pathways were the most significantly enriched KEGG pathways. Reverse transcription-polymerase chain reaction analysis and immunohistochemistry were performed to validate further the differential expression patterns of representative genes. The reported results in this study provide the basis for elucidating the molecular mechanisms for silica-induced pulmonary inflammation and fibrosis, and support the prevention and treatment of silicosis.Silicosis mice model was established by intra-tracheal instillation of silica suspensions. High-throughput RNA-Seq and DGE analysis revealed 749 up-regulated and 70 down-regulated genes. Genes related to immune cell interactions, immune cell responses and inflammation were significantly enriched. Cytokine-cytokine receptor interaction and down-stream JAK-STAT signalling pathways were significantly enriched KEGG pathways. The reported results in this study provide basis for elucidating the molecular mechanisms for silica induced pulmonary inflammation and fibrosis, and support the prevention and treatment of silicosis.