miR-138 inhibits epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by regulating ZEB2
miR-138 inhibits epithelial-mesenchymal transition in silica-induced pulmonary fibrosis by regulating ZEB2
复制标题
miR-138通过调节ZEB2抑制二氧化硅诱导的肺纤维化中的上皮间质转化
DOI：
10.1016/j.tox.2021.152925
复制
发表时间：
2021-09-04
期刊：
影响因子：
4.5
通讯作者：
Wang, Feng
中科院分区：
文献类型：
--
作者：
Wu, Qiuyun;Gui, Wenwen;Wang, Feng
硅尘是煤矿等职业环境中常见的污染物。吸入矽尘可引起进行性肺纤维化，进而引起矽肺。矽肺仍是世界上危害最大的职业病之一，因此研究其发病机制对矽肺的治疗是必要的。在这项研究中，我们通过肺内滴注二氧化硅颗粒构建了小鼠肺纤维化模型，并鉴定了miR-138在小鼠纤维化肺组织中的表达降低。此外，在二氧化硅颗粒暴露和二氧化硅颗粒刺激的上皮细胞的小鼠模型中，miR-138的过表达延缓了上皮-间充质转化（EMT）的过程。进一步的研究表明，ZEB 2是miR-138的潜在靶点之一，miR-138的上调降低了小鼠肺组织和上皮细胞中的ZEB 2水平。我们接下来发现，在上皮细胞中转染miR-138抑制剂后，α-SMA和波形蛋白的表达水平显著增加，E-钙粘蛋白水平降低。然而，这些作用被ZEB 2的敲低减弱。一致地，通过miR 138抑制剂转染增加的上皮细胞的迁移能力也通过ZEB 2的敲低逆转。总的来说，我们发现miR-138显著靶向ZEB 2，从而抑制EMT过程并减轻肺纤维化的发展。miR-138可能是治疗肺纤维化的潜在靶点。
Silica dust is a common pollutant in the occupational environment, such as coal mines. Inhalation of silica dust can cause progressive pulmonary fibrosis and then silicosis. Silicosis is still one of the most harmful occupational diseases in the world, so the study of its pathogenesis is necessary for the treatment of silicosis. In this study, we constructed a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles and identified the decreased expression of miR-138 in fibrotic lung tissues of mice. Moreover, the overexpression of miR-138 retarded the process of epithelial-mesenchymal transition (EMT) in a mouse model of silica particles exposure and epithelial cells stimulated by silica particles. Further studies showed that ZEB2 was one of the potential targets of miR-138, and the up-regulation of miR-138 reduced ZEB2 levels in mouse lung tissues and in epithelial cells. We next found that the expression levels of alpha-SMA and Vimentin were significantly increased and E-cadherin levels were decreased after transfection with miR-138 inhibitor in epithelial cells. However, these effects were abated by the knockdown of ZEB2. Consistently, the increased migration ability of epithelial cells by miR138 inhibitor transfection was also reversed by the knockdown of ZEB2. Collectively, we revealed that miR-138 significantly targeted ZEB2, thus inhibited the EMT process and mitigated the development of pulmonary fibrosis. miR-138 may be a potential target for the treatment of pulmonary fibrosis.