Snail-mediated partial epithelial mesenchymal transition augments the differentiation of local lung myofibroblast.
Snail-mediated partial epithelial mesenchymal transition augments the differentiation of local lung myofibroblast.
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蜗牛介导的部分上皮间充质转化促进局部肺肌成纤维细胞分化。
DOI：
10.1016/j.chemosphere.2020.128870
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发表时间：
2020-11
期刊：
影响因子：
8.8
通讯作者：
Yan Wang;Siling Li;J. Zhao;Qiuyue Li;Chunjie Xu;Huihui Wu;Zhonghui Zhu;L. Tian
中科院分区：
文献类型：
--
作者：
Yan Wang;Siling Li;J. Zhao;Qiuyue Li;Chunjie Xu;Huihui Wu;Zhonghui Zhu;L. Tian
肺纤维化疾病的发病机制被认为与环境暴露有关，但具体机制尚不清楚，也没有有效的治疗方法。上皮间质转化（EMT）对肺纤维化的贡献一直存在争议。研究发现部分EMT可能在肾纤维化过程中发挥重要作用。我们还发现部分EMT可能与纤维化疾病有关。本研究利用矽肺肺纤维化动物模型观察肺纤维化疾病中是否存在部分EMT，并通过TGF-β1刺激的成纤维细胞和肺泡上皮细胞共培养系统来评估部分EMT的可能作用，从而确定部分EMT在肺纤维化疾病中的可能作用。在体内，结果表明二氧化硅诱导的肺纤维化模型中可能存在部分EMT，而Snail（一种有效的EMT诱导剂）参与了这一过程。在体外，共培养系统用于评估小鼠肺泡上皮 II 型 (ATII) 细胞中 EMT 对小鼠肺成纤维细胞活化为肌成纤维细胞的影响。结果表明，经历EMT的上皮细胞促进肺肌成纤维细胞的分化，这种上皮-间质串扰主要由Snail控制。 Snail沉默后，EMT和NIH-3T3向肌成纤维细胞的激活均受到明显抑制。这表明针对这种新型 Snail 可能是治疗肺纤维化疾病的可行策略。
The pathogenesis of pulmonary fibrosis diseases is considered to be related with environmental exposures, but the exact mechanism is unclear and there are no effective treatments. The contribution of epithelial-mesenchymal transition (EMT) to lung fibrosis has been controversial. It was found that partial EMT might play a vital role in renal fibrosis. We also found that partial EMT might be involved in fibrosis diseases. In this study, we used a silicosis animal model of pulmonary fibrosis to observe whether partial EMT existed in pulmonary fibrosis disease and a co-culture system culturing fibroblasts and alveolar epithelial cells stimulated by TGF-β1 to evaluate the probable effects of partial EMT, thus determined the probable role of partial EMT in pulmonary fibrosis diseases. In vivo, the results revealed that partial EMT might exist in silica-induced lung fibrosis model and Snail which is a potent EMT inducer was involved during the process. In vitro, a co-culture system was used to evaluate the effects of EMT in murine alveolar epithelial type II (ATII) cells on the activation of underlying murine lung fibroblasts into myofibroblasts. The results showed that epithelial cells undergoing EMT promoted the differentiation of lung myofibroblast and this epithelial-mesenchymal crosstalk was mainly controlled by Snail. Following Snail silencing the EMT and the activation of NIH-3T3 into myofibroblast were obviously inhibited. It indicated that targeting this novel Snail might be a viable strategy for the treatment of lung fibrosis diseases.