Role of MCPIP1 in the Endothelial-Mesenchymal Transition Induced by Silica
Role of MCPIP1 in the Endothelial-Mesenchymal Transition Induced by Silica
复制标题
MCPIP1 在二氧化硅诱导的内皮-间质转化中的作用。
DOI：
10.1159/000452547
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Yao, Honghong
中科院分区：
文献类型：
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作者：
Chao, Jie;Wang, Xingang;Yao, Honghong
背景：矽肺的特点是成纤维细胞堆积和细胞外基质过度沉积。通过内皮-间质转化（EndMT）生成成纤维细胞是导致成纤维细胞积累的一个过程。然而，EndMT 的潜在机制仍然未知。方法：将人脐静脉内皮细胞（HUVEC）暴露于SiO2（50 μg/cm(2)）中。使用免疫荧光和蛋白质印迹分析评估特异性内皮和间质标记物。通过分析细胞迁移和增殖来评估功能变化。进行LC3腺病毒转染，并使用自噬标记物测量自噬的变化。结果：SiO2 诱导 HUVEC 中内皮细胞特异性标记物的减少，同时显着增加间充质细胞产物水平和间充质功能。尽管MCPIP1表达随着特定间充质细胞产物的增加而增加，但MCPIP1表达水平与观察到的特定内皮标志物表达的减少并不一致。自噬介导了 MCPIP1 的作用，雷帕霉素和 3-MA 分别增强和减弱了 SiO2 对 HUVEC 的作用。 MAPKs 和 PI3K/Akt 通路参与 SiO2 对 MCPIP1 的调节，以及 Pyk2 和 MLC-2 介导的细胞迁移。结论：我们的研究结果揭示了 MCPIP1 的新潜在功能，提示了肺矽肺纤维化的可能机制。 (C) 2016 作者由巴塞尔 S. Karger AG 出版
Background: Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 mu g/cm(2)). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis. Functional changes were evaluated by analyzing cell migration and proliferation. LC3-adenovirus transfections were performed, and changes in autophagy were measured using a marker of autophagy. Results: SiO2 induced decreases in the endothelial cell-specific markers in HUVECs while dramatically increasing mesenchymal cell product levels and mesenchymal functions. Although MCPIP1 expression increased in parallel with the increase in specific mesenchymal cell products, the MCPIP1 expression level was not consistent with the observed decrease in specific endothelial marker expression. Autophagy mediated the effects of MCPIP1, as rapamycin and 3-MA enhanced and attenuated the effect of SiO2 on HUVECs, respectively. MAPKs and the PI3K/Akt pathway were involved in the regulation of MCPIP1 by SiO2, and Pyk2 and MLC-2 mediated cell migration. Conclusion: Our findings reveal a new potential function of MCPIP1, suggesting a possible mechanism of fibrosis in pulmonary silicosis. (C) 2016 The Author(s) Published by S. Karger AG, Basel