Long non-coding RNA SNHG1 promotes fibroblast-to-myofibroblast transition during the development of pulmonary fibrosis induced by silica particles exposure
Long non-coding RNA SNHG1 promotes fibroblast-to-myofibroblast transition during the development of pulmonary fibrosis induced by silica particles exposure
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长非编码RNA SNHG1在二氧化硅颗粒暴露诱导的肺纤维化发展过程中促进成纤维细胞向肌成纤维细胞的转变
DOI：
10.1016/j.ecoenv.2021.112938
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发表时间：
2021
影响因子：
6.8
通讯作者：
Han Lei
中科院分区：
文献类型：
--
作者：
Wu Qiuyun;Jiao Biyang;Gui Wenwen;Zhang Qianyi;Wang Feng;Han Lei
吸入环境中的二氧化硅粉尘可导致进行性肺纤维化，然后是矽肺。矽肺是世界上危害最大的职业病，因此研究其发病机制对矽肺的防治具有重要意义。长链非编码RNA（lncRNA）在纤维化疾病的病理过程中起重要作用。然而，特异性lncRNA在调节肺纤维化中的功能仍然是难以捉摸的。本研究通过肺内滴入二氧化硅颗粒建立小鼠肺纤维化模型，采用qRT-PCR方法检测肺组织和TGF-β1处理的成纤维细胞中nc-SNHG 1和miR-326的差异表达。设计短干扰RNA（siRNA）和质粒用于敲低或过表达成纤维细胞中的flnc-SNHG 1。设计用于在体内和体外过表达miR-326的miRNA模拟物。采用双荧光素酶报告系统、免疫荧光、western blot、创伤愈合和transwell实验等方法研究nc-SNHG 1的功能和作用机制。结果发现，lnc-SNHG 1在小鼠肺纤维化组织和TGF-β1处理的成纤维细胞中高表达。高表达nc-SNHG 1促进成纤维细胞的迁移、侵袭和纤维化分子的分泌，而低表达nc-SNHG 1则相反。进一步的机制研究表明，miR-326是flnc-SNHG 1的潜在靶点，且flnc-SNHG 1与miR-326的表达水平呈负相关。结合减轻miR-326在二氧化硅颗粒暴露小鼠模型中的纤维化作用，我们发现lnc-SNHG 1显著海绵化miR-326并促进SP1的表达，从而加速成纤维细胞向肌成纤维细胞的转化并协同促进肺纤维化的发展。我们的研究揭示了lnc-SNHG 1通过miR-326/SP1轴调控肺纤维化的关键机制，lnc-SNHG 1是防治矽肺的潜在靶点。
Inhaling silica dust in the environment can cause progressive pulmonary fibrosis, then silicosis. Silicosis is the most harmful occupational disease in the world, so the study of the mechanism is of great significance for the prevention and treatment of silicosis. Long non-coding RNAs (lncRNAs) are important players in the pathological process of fibrotic diseases. However, the function of specific lncRNA in regulating pulmonary fibrosis remains elusive. In this study, a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles was established, and the differential expression oflnc-SNHG1and miR-326 in lung tissues and TGF-β1-treated fibroblasts was detected by the qRT-PCR method. Short interfering RNA (siRNA) and plasmid were designed for knockdown or overexpression oflnc-SNHG1in fibroblasts. MiRNA simulant was designed for overexpression of miR-326 in vivo and in vitro. Dual-luciferase reporter system, immunofluorescence, western blot, wound healing and transwell assay were performed to investigate the function and the underlying mechanisms oflnc-SNHG1. As a result, we found thatlnc-SNHG1was highly expressed in fibrotic lung tissues of mice and TGF-β1-treated fibroblasts. Moreover, the high expression oflnc-SNHG1facilitated the migration and invasion of fibroblasts and the secretion of fibrotic molecules, while the low expression oflnc-SNHG1exerted the opposite effects. Further mechanism studies showed that miR-326 was the potential target oflnc-SNHG1, and there is a negative correlation between the expression levels oflnc-SNHG1and miR-326. Combined with mitigating fibrotic effects of miR-326 in a mouse model of silica particles exposure, we revealed thatlnc-SNHG1significantly sponged miR-326 and facilitated the expression of SP1, thus accelerating fibroblast-to-myofibroblast transition and synergistically promoting the development of pulmonary fibrosis. Our study uncovered a key mechanism by whichlnc-SNHG1regulated pulmonary fibrosis through miR-326/SP1 axis, andlnc-SNHG1is a potential target for the prevention and treatment of silicosis.