MicroRNA-29b Mediates Lung Mesenchymal-Epithelial Transition and Prevents Lung Fibrosis in the Silicosis Model
MicroRNA-29b Mediates Lung Mesenchymal-Epithelial Transition and Prevents Lung Fibrosis in the Silicosis Model
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MicroRNA-29b 介导硅肺模型中的肺间质-上皮转化并预防肺纤维化
DOI：
10.1016/j.omtn.2018.10.017
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发表时间：
2019-03-01
影响因子：
8.8
通讯作者：
Tian, Lin
中科院分区：
文献类型：
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作者：
Sun, Jingping;Li, Qiuyue;Tian, Lin
肺上皮间质转化（EMT）在矽肺纤维化中起重要作用。EMT的逆转过程是间充质-上皮转化（MET），MET被视为抗EMT疗法，并且是纤维化的良好靶点。microRNA（miRNAs）已成为EMT和MET程序的有效调节因子，因此，我们使用微阵列测定来测试miRNAs表达，并研究它们在二氧化硅诱导的肺上皮细胞EMT中的作用。我们发现miRNA-29 b（miR-29 b）在RLE-6 TN细胞中被二氧化硅动态下调并影响MET的促进。此外，向小鼠递送miR-29 b显著抑制二氧化硅诱导的EMT，预防肺纤维化，并改善肺功能。总之，我们的研究结果清楚地表明，miR-29 b可能通过促进MET和抑制肺中的EMT，作为硅肺纤维化抑制肺纤维化的新型负调节因子。这些发现可能代表了治疗矽肺纤维化的新的潜在治疗靶点。
Lung epithelial-mesenchymal transition (EMT) plays an important role in silicosis fibrosis. The reverse process of EMT is mesenchymal-epithelial transition (MET), which is viewed as an anti-EMT therapy and is a good target toward fibrosis. MicroRNAs (miRNAs) have emerged as potent regulators of EMT and MET programs, and, hence, we tested the miRNA expression using microarray assay and investigated their roles in silica-induced EMT in lung epithelial cells. We found that miRNA-29b (miR-29b) was dynamically downregulated by silica and influenced the promotion of MET in RLE-6TN cells. Furthermore, delivery of miR-29b to mice significantly inhibited silica-induced EMT, prevented lung fibrosis, and improved lung function. Together, our results clearly demonstrated that miR-29b acted as a novel negative regulator of silicosis fibrosis-inhibited lung fibrosis, probably by promoting MET and by suppressing EMT in the lung. These findings may represent a new potential therapeutic target for treating silicosis fibrosis.